Academic Appointments

Honors & Awards

  • Early Career Life Scientist Award, American Society for Cell Biology (2011)
  • Searle Scholar, Searle Scholar Program (2010-2013)
  • Fellowship Award in the Neurosciences, The Esther A. & Joseph Klingenstein Fund (2009-2012)
  • Sloan Research Fellowship, Alfred P. Sloan Foundation (2009-2011)
  • Basil O'Connor Award, March of Dimes (2009-2011)
  • Scientist Development Award, American Heart Association (2009-2012)
  • Career Development Award, AACR-Pancreatic Cancer Action Network (2009-2011)
  • Frederick E. Terman Fellow, Stanford University (2008-2011)
  • Postdoctoral Fellowship, Damon Runyon Cancer Research Foundation (2003-2005)
  • Ph.D. Fellowship, Boehringer Ingelheim Foundation (1998-2001)

Professional Education

  • Postdoc, Genentech, Cell Biology and Biochemistry (2007)
  • Ph.D., UC Berkeley and Université Paris-Orsay, Molecular and Cellular Biology (2001)
  • B.Sc., Ecole Normale Supérieure (Paris), Biology and Biochemistry (1997)

Research & Scholarship

Current Research and Scholarly Interests

Our laboratory investigates the molecular principles of primary cilium assembly and function. Shaped like an antenna projecting out of the cell, the primary cilium exposes receptors for diverse stimuli (like platelet-derived growth factors, Hedgehog morphogens and olfactory cues) and concentrates their downstream signaling machinery to send specific molecular responses back into the cell. Despite these fascinating properties, the cilium has historically been the least studied cellular organelle and most of the fundamental questions concerning cilium biogenesis and function remain unanswered. Nowhere is our knowledge gap more striking than for the ciliopathies, a class of inherited disorders of the cilium whose central features include obesity, kidney malformations and retinal degeneration. We thus intend to uncover the molecular machines that build cilia and convey information into and out of cilia by applying proteomics, cellular imaging and in vitro reconstitution assays to entry points provided by human genetics.

The central projects of the lab currently are "Trafficking of signaling receptors to the primary cilium" and "Functional roles of the tubulin code"


2013-14 Courses

Graduate and Fellowship Programs


Journal Articles

  • An in vitro assay for entry into cilia reveals unique properties of the soluble diffusion barrier JOURNAL OF CELL BIOLOGY Breslow, D. K., Koslover, E. F., Seydel, F., Spakowitz, A. J., Nachury, M. V. 2013; 203 (1): 129-147


    Specific proteins are concentrated within primary cilia, whereas others remain excluded. To understand the mechanistic basis of entry into cilia, we developed an in vitro assay using cells in which the plasma membrane was permeabilized, but the ciliary membrane was left intact. Using a diffusion-to-capture system and quantitative analysis, we find that proteins >9 nm in diameter (∼100 kD) are restricted from entering cilia, and we confirm these findings in vivo. Interference with the nuclear pore complex (NPC) or the actin cytoskeleton in permeabilized cells demonstrated that the ciliary diffusion barrier is mechanistically distinct from those of the NPC or the axon initial segment. Moreover, applying a mass transport model to this system revealed diffusion coefficients for soluble and membrane proteins within cilia that are compatible with rapid exploration of the ciliary space in the absence of active transport. Our results indicate that large proteins require active transport for entry into cilia but not necessarily for movement inside cilia.

    View details for DOI 10.1083/jcb.201212024

    View details for Web of Science ID 000325742200013

    View details for PubMedID 24100294

  • Single molecule imaging reveals a major role for diffusion in the exploration of ciliary space by signaling receptors. eLife Ye, F., Breslow, D. K., Koslover, E. F., Spakowitz, A. J., Nelson, W. J., Nachury, M. V. 2013; 2


    The dynamic organization of signaling cascades inside primary cilia is key to signal propagation. Yet little is known about the dynamics of ciliary membrane proteins besides a possible role for motor-driven Intraflagellar Transport (IFT). To characterize these dynamics, we imaged single molecules of Somatostatin Receptor 3 (SSTR3, a GPCR) and Smoothened (Smo, a Hedgehog signal transducer) in the ciliary membrane. While IFT trains moved processively from one end of the cilium to the other, single SSTR3 and Smo underwent mostly diffusive behavior interspersed with short periods of directional movements. Statistical subtraction of instant velocities revealed that SSTR3 and Smo spent less than a third of their time undergoing active transport. Finally, SSTR3 and IFT movements could be uncoupled by perturbing either membrane protein diffusion or active transport. Thus ciliary membrane proteins move predominantly by diffusion, and attachment to IFT trains is transient and stochastic rather than processive or spatially determined. DOI:

    View details for DOI 10.7554/eLife.00654

    View details for PubMedID 23930224

  • The Conserved Bardet-Biedl Syndrome Proteins Assemble a Coat that Traffics Membrane Proteins to Cilia CELL Jin, H., White, S. R., Shida, T., Schulz, S., Aguiar, M., Gygi, S. P., Bazan, J. F., Nachury, M. V. 2010; 141 (7): 1208-U198


    The BBSome is a complex of Bardet-Biedl Syndrome (BBS) proteins that shares common structural elements with COPI, COPII, and clathrin coats. Here, we show that the BBSome constitutes a coat complex that sorts membrane proteins to primary cilia. The BBSome is the major effector of the Arf-like GTPase Arl6/BBS3, and the BBSome and GTP-bound Arl6 colocalize at ciliary punctae in an interdependent manner. Strikingly, Arl6(GTP)-mediated recruitment of the BBSome to synthetic liposomes produces distinct patches of polymerized coat apposed onto the lipid bilayer. Finally, the ciliary targeting signal of somatostatin receptor 3 needs to be directly recognized by the BBSome in order to mediate targeting of membrane proteins to cilia. Thus, we propose that trafficking of BBSome cargoes to cilia entails the coupling of BBSome coat polymerization to the recognition of sorting signals by the BBSome.

    View details for DOI 10.1016/j.cell.2010.05.015

    View details for Web of Science ID 000279148100017

    View details for PubMedID 20603001

  • Exome sequencing of Bardet-Biedl syndrome patient identifies a null mutation in the BBSome subunit BBIP1 (BBS18) JOURNAL OF MEDICAL GENETICS Scheidecker, S., Etard, C., Pierce, N. W., Geoffroy, V., Schaefer, E., Muller, J., Chennen, K., Flori, E., Pelletier, V., Poch, O., Marion, V., Stoetzel, C., Straehle, U., Nachury, M. V., Dollfus, H. 2014; 51 (2): 132-136


    Bardet-Biedl syndrome (BBS) is a recessive and genetically heterogeneous ciliopathy characterised by retinitis pigmentosa, obesity, kidney dysfunction, postaxial polydactyly, behavioural dysfunction and hypogonadism. 7 of the 17 BBS gene products identified to date assemble together with the protein BBIP1/BBIP10 into the BBSome, a protein complex that ferries signalling receptors to and from cilia.Exome sequencing performed on a sporadic BBS case revealed for the first time a homozygous stop mutation (NM_001195306: c.173T>G, p.Leu58*) in the BBIP1 gene. This mutation is pathogenic since no BBIP1 protein could be detected in fibroblasts from the patient, and BBIP1[Leu58*] is unable to associate with the BBSome subunit BBS4.These findings identify BBIP1 as the 18th BBS gene (BBS18) and suggest that BBSome assembly may represent a unifying pathomechanism for BBS.

    View details for DOI 10.1136/jmedgenet-2013-101785

    View details for Web of Science ID 000331191300009

    View details for PubMedID 24026985

  • Effects of tubulin acetylation and tubulin acetyltransferase binding on microtubule structure MOLECULAR BIOLOGY OF THE CELL Howes, S. C., Alushin, G. M., Shida, T., Nachury, M. V., Nogales, E. 2014; 25 (2): 257-266


    Tubulin undergoes posttranslational modifications proposed to specify microtubule subpopulations for particular functions. Most of these modifications occur on the C-termini of tubulin and may directly affect the binding of microtubule-associated proteins (MAPs) or motors. Acetylation of Lys-40 on α-tubulin is unique in that it is located on the luminal surface of microtubules, away from the interaction sites of most MAPs and motors. We investigate whether acetylation alters the architecture of microtubules or the conformation of tubulin, using cryo-electron microscopy (cryo-EM). No significant changes are observed based on protofilament distributions or microtubule helical lattice parameters. Furthermore, no clear differences in tubulin structure are detected between cryo-EM reconstructions of maximally deacetylated or acetylated microtubules. Our results indicate that the effect of acetylation must be highly localized and affect interaction with proteins that bind directly to the lumen of the microtubule. We also investigate the interaction of the tubulin acetyltransferase, αTAT1, with microtubules and find that αTAT1 is able to interact with the outside of the microtubule, at least partly through the tubulin C-termini. Binding to the outside surface of the microtubule could facilitate access of αTAT1 to its luminal site of action if microtubules undergo lateral opening between protofilaments.

    View details for DOI 10.1091/mbc.E13-07-0387

    View details for Web of Science ID 000330022900005

    View details for PubMedID 24227885

  • Cilia Grow by Taking a Bite out of the Cell. Developmental cell Pierce, N. W., Nachury, M. V. 2013; 27 (2): 126-127


    Autophagy and primary cilium assembly have long been known to be induced by the same conditions in cultured cells. Two recent studies in Nature-Tang et al. (2013) and Pampliega et al. (2013)-link the two processes, suggesting that a specialized autophagy pathway near the basal body regulates cilium assembly.

    View details for DOI 10.1016/j.devcel.2013.10.013

    View details for PubMedID 24176638

  • alpha TAT1 catalyses microtubule acetylation at clathrin-coated pits NATURE Montagnac, G., Meas-Yedid, V., Irondelle, M., Castro-Castro, A., Franco, M., Shida, T., Nachury, M. V., Benmerah, A., Olivo-Marin, J., Chavrier, P. 2013; 502 (7472): 567-?


    In most eukaryotic cells microtubules undergo post-translational modifications such as acetylation of α-tubulin on lysine 40, a widespread modification restricted to a subset of microtubules that turns over slowly. This subset of stable microtubules accumulates in cell protrusions and regulates cell polarization, migration and invasion. However, mechanisms restricting acetylation to these microtubules are unknown. Here we report that clathrin-coated pits (CCPs) control microtubule acetylation through a direct interaction of the α-tubulin acetyltransferase αTAT1 (refs 8, 9) with the clathrin adaptor AP2. We observe that about one-third of growing microtubule ends contact and pause at CCPs and that loss of CCPs decreases lysine 40 acetylation levels. We show that αTAT1 localizes to CCPs through a direct interaction with AP2 that is required for microtubule acetylation. In migrating cells, the polarized orientation of acetylated microtubules correlates with CCP accumulation at the leading edge, and interaction of αTAT1 with AP2 is required for directional migration. We conclude that microtubules contacting CCPs become acetylated by αTAT1. In migrating cells, this mechanism ensures the acetylation of microtubules oriented towards the leading edge, thus promoting directional cell locomotion and chemotaxis.

    View details for DOI 10.1038/nature12571

    View details for Web of Science ID 000325988400058

    View details for PubMedID 24097348

  • Structure of the alpha-tubulin acetyltransferase, alpha TAT1, and implications for tubulin-specific acetylation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Friedmann, D. R., Aguilar, A., Fan, J., Nachury, M. V., Marmorstein, R. 2012; 109 (48): 19655-19660


    Protein acetylation is an important posttranslational modification with the recent identification of new substrates and enzymes, new links to disease, and modulators of protein acetylation for therapy. ?-Tubulin acetyltransferase (?TAT1) is the major ?-tubulin lysine-40 (K40) acetyltransferase in mammals, nematodes, and protozoa, and its activity plays a conserved role in several microtubule-based processes. Here, we present the X-ray crystal structure of the human ?TAT1/acetyl-CoA complex. Together with structure-based mutagenesis, enzymatic analysis, and functional studies in cells, we elucidate the catalytic mechanism and mode of tubulin-specific acetylation. We find that ?TAT1 has an overall fold similar to the Gcn5 histone acetyltransferase but contains a relatively wide substrate binding groove and unique structural elements that play important roles in ?-tubulin-specific acetylation. Conserved aspartic acid and cysteine residues play important catalytic roles through a ternary complex mechanism. ?TAT1 mutations have analogous effects on tubulin acetylation in vitro and in cells, demonstrating that it is the central determining factor of ?-tubulin K40 acetylation levels in vivo. Together, these studies provide general insights into distinguishing features between histone and tubulin acetyltransferases, and they have specific implications for understanding the molecular basis of tubulin acetylation and for developing small molecule modulators of microtubule acetylation for therapy.

    View details for DOI 10.1073/pnas.1209357109

    View details for Web of Science ID 000312313900037

    View details for PubMedID 23071314

  • A Novel Protein LZTFL1 Regulates Ciliary Trafficking of the BBSome and Smoothened PLOS GENETICS Seo, S., Zhang, Q., Bugge, K., Breslow, D. K., Searby, C. C., Nachury, M. V., Sheffield, V. C. 2011; 7 (11)


    Many signaling proteins including G protein-coupled receptors localize to primary cilia, regulating cellular processes including differentiation, proliferation, organogenesis, and tumorigenesis. Bardet-Biedl Syndrome (BBS) proteins are involved in maintaining ciliary function by mediating protein trafficking to the cilia. However, the mechanisms governing ciliary trafficking by BBS proteins are not well understood. Here, we show that a novel protein, Leucine-zipper transcription factor-like 1 (LZTFL1), interacts with a BBS protein complex known as the BBSome and regulates ciliary trafficking of this complex. We also show that all BBSome subunits and BBS3 (also known as ARL6) are required for BBSome ciliary entry and that reduction of LZTFL1 restores BBSome trafficking to cilia in BBS3 and BBS5 depleted cells. Finally, we found that BBS proteins and LZTFL1 regulate ciliary trafficking of hedgehog signal transducer, Smoothened. Our findings suggest that LZTFL1 is an important regulator of BBSome ciliary trafficking and hedgehog signaling.

    View details for DOI 10.1371/journal.pgen.1002358

    View details for Web of Science ID 000297264500013

    View details for PubMedID 22072986

  • The major alpha-tubulin K40 acetyltransferase alpha TAT1 promotes rapid ciliogenesis and efficient mechanosensation PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Shida, T., Cueva, J. G., Xu, Z., Goodman, M. B., Nachury, M. V. 2010; 107 (50): 21517-21522


    Long-lived microtubules found in ciliary axonemes, neuronal processes, and migrating cells are marked by ?-tubulin acetylation on lysine 40, a modification that takes place inside the microtubule lumen. The physiological importance of microtubule acetylation remains elusive. Here, we identify a BBSome-associated protein that we name ?TAT1, with a highly specific ?-tubulin K40 acetyltransferase activity and a catalytic preference for microtubules over free tubulin. In mammalian cells, the catalytic activity of ?TAT1 is necessary and sufficient for ?-tubulin K40 acetylation. Remarkably, ?TAT1 is universally and exclusively conserved in ciliated organisms, and is required for the acetylation of axonemal microtubules and for the normal kinetics of primary cilium assembly. In Caenorhabditis elegans, microtubule acetylation is most prominent in touch receptor neurons (TRNs) and MEC-17, a homolog of ?TAT1, and its paralog ?TAT-2 are required for ?-tubulin acetylation and for two distinct types of touch sensation. Furthermore, in animals lacking MEC-17, ?TAT-2, and the sole C. elegans K40?-tubulin MEC-12, touch sensation can be restored by expression of an acetyl-mimic MEC-12[K40Q]. We conclude that ?TAT1 is the major and possibly the sole ?-tubulin K40 acetyltransferase in mammals and nematodes, and that tubulin acetylation plays a conserved role in several microtubule-based processes.

    View details for DOI 10.1073/pnas.1013728107

    View details for Web of Science ID 000285521500055

    View details for PubMedID 21068373

  • A Septin Diffusion Barrier at the Base of the Primary Cilium Maintains Ciliary Membrane Protein Distribution SCIENCE Hu, Q., Milenkovic, L., Jin, H., Scott, M. P., Nachury, M. V., Spiliotis, E. T., Nelson, W. J. 2010; 329 (5990): 436-439


    In animal cells, the primary cilium transduces extracellular signals through signaling receptors localized in the ciliary membrane, but how these ciliary membrane proteins are retained in the cilium is unknown. We found that ciliary membrane proteins were highly mobile, but their diffusion was impeded at the base of the cilium by a diffusion barrier. Septin 2 (SEPT2), a member of the septin family of guanosine triphosphatases that form a diffusion barrier in budding yeast, localized at the base of the ciliary membrane. SEPT2 depletion resulted in loss of ciliary membrane protein localization and Sonic hedgehog signal transduction, and inhibited ciliogenesis. Thus, SEPT2 is part of a diffusion barrier at the base of the ciliary membrane and is essential for retaining receptor-signaling pathways in the primary cilium.

    View details for DOI 10.1126/science.1191054

    View details for Web of Science ID 000280196500036

    View details for PubMedID 20558667

  • Trafficking to the Ciliary Membrane: How to Get Across the Periciliary Diffusion Barrier? ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, VOL 26 Nachury, M. V., Seeley, E. S., Jin, H. 2010; 26: 59-87


    The primary cilium organizes numerous signal transduction cascades, and an understanding of signaling receptor trafficking to cilia is now emerging. A defining feature of cilia is the periciliary diffusion barrier that separates the ciliary and plasma membranes. Although lateral transport through this barrier may take place, polarized exocytosis to the base of the cilium has been the prevailing model for delivering membrane proteins to cilia. Key players for this polarized exocytosis model include the GTPases Rab8 and Rab11, the exocyst, and possibly the intraflagellar tranport machinery. In turn, the sorting of membrane proteins to cilia critically relies on the recognition of ciliary targeting signals by sorting machines such as the BBSome coat complex or the GTPase Arf4. Finally, some proteins need to exit from cilia, and ubiquitination may regulate this step. The stage is now set to dissect the interplay between signaling and regulated trafficking to and from cilia.

    View details for DOI 10.1146/annurev.cellbio.042308.113337

    View details for Web of Science ID 000284856700003

    View details for PubMedID 19575670

  • The BBSome CURRENT BIOLOGY Jin, H., Nachury, M. V. 2009; 19 (12): R472-R473

    View details for Web of Science ID 000267338500008

    View details for PubMedID 19549489

  • A BBSome Subunit Links Ciliogenesis, Microtubule Stability, and Acetylation DEVELOPMENTAL CELL Loktev, A. V., Zhang, Q., Beck, J. S., Searby, C. C., Scheetz, T. E., Bazan, J. F., Slusarski, D. C., Sheffield, V. C., Jackson, P. K., Nachury, M. V. 2008; 15 (6): 854-865


    Primary cilium dysfunction affects the development and homeostasis of many organs in Bardet-Biedl syndrome (BBS). We recently showed that seven highly conserved BBS proteins form a stable complex, the BBSome, that functions in membrane trafficking to and inside the primary cilium. We have now discovered a BBSome subunit that we named BBIP10. Similar to other BBSome subunits, BBIP10 localizes to the primary cilium, BBIP10 is present exclusively in ciliated organisms, and depletion of BBIP10 yields characteristic BBS phenotypes in zebrafish. Unexpectedly, BBIP10 is required for cytoplasmic microtubule polymerization and acetylation, two functions not shared with any other BBSome subunits. Strikingly, inhibition of the tubulin deacetylase HDAC6 restores microtubule acetylation in BBIP10-depleted cells, and BBIP10 physically interacts with HDAC6. BBSome-bound BBIP10 may therefore function to couple acetylation of axonemal microtubules and ciliary membrane growth.

    View details for DOI 10.1016/j.devcel.2008.11.001

    View details for Web of Science ID 000261631500009

    View details for PubMedID 19081074

  • Tandem affinity purification of the BBSome, a critical regulator of Rab8 in ciliogenesis SMALL GTPASES IN DISEASE, PT B Nachury, M. V. 2008; 439: 501-?


    Bardet-Biedl syndrome (BBS) is a hereditary disorder whose symptoms include obesity, retinal degeneration, and kidney cysts. Intriguingly, the cellular culprit of BBS seems to lie in the primary cilium, a "cellular antenna" used by a number of signaling pathways. Yet, despite the identification of 12 BBS genes, a consistent molecular pathway for BBS had so far remained elusive. The recent discovery of a stable complex of seven BBS proteins (the BBSome) considerably simplifies the apparent molecular complexity of BBS and provides a clear insight into the molecular basis of BBS. Most tellingly, the BBSome associates with Rabin8, the guanine nucleotide exchange factor for the small GTPase Rab8, and Rab8-GTP enters the primary cilium to promote extension of the ciliary membrane. Thus, BBS is likely caused by defects in vesicular transport to the primary cilium. This chapter describes methods used to purify the BBSome using a tandem affinity purification method and presents a variation of this technique to demonstrate the existence of a stable complex of BBS proteins by sucrose gradient fractionation. When combined with state-of-the art mass spectrometry, these methods can provide a nearly complete BBSome interactome containing factors such as Rabin8.

    View details for DOI 10.1016/S0076-6879(07)00434-X

    View details for Web of Science ID 000255021300034

    View details for PubMedID 18374185

  • A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis CELL Nachury, M. V., Loktev, A. V., Zhang, Q., Westlake, C. J., Peranen, J., Merdes, A., Slusarski, D. C., Scheller, R. H., Bazan, J. F., Sheffield, V. C., Jackson, P. K. 2007; 129 (6): 1201-1213


    Primary cilium dysfunction underlies the pathogenesis of Bardet-Biedl syndrome (BBS), a genetic disorder whose symptoms include obesity, retinal degeneration, and nephropathy. However, despite the identification of 12 BBS genes, the molecular basis of BBS remains elusive. Here we identify a complex composed of seven highly conserved BBS proteins. This complex, the BBSome, localizes to nonmembranous centriolar satellites in the cytoplasm but also to the membrane of the cilium. Interestingly, the BBSome is required for ciliogenesis but is dispensable for centriolar satellite function. This ciliogenic function is mediated in part by the Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Strikingly, Rab8(GTP) enters the primary cilium and promotes extension of the ciliary membrane. Conversely, preventing Rab8(GTP) production blocks ciliation in cells and yields characteristic BBS phenotypes in zebrafish. Our data reveal that BBS may be caused by defects in vesicular transport to the cilium.

    View details for DOI 10.1016/j.cell.2007.03.053

    View details for Web of Science ID 000247390400022

    View details for PubMedID 17574030

  • A Rae1-containing ribonucleoprotein complex is required for mitotic spindle assembly Cell Blower MD*, Nachury MV*, Heald R, Weis K 2005; 121 (2): 223-234
  • Importin beta is a mitotic target of the small GTPase ran in spindle assembly CELL Nachury, M. V., Maresca, T. J., Salmon, W. G., Waterman-Storer, C. M., Heald, R., Weis, K. 2001; 104 (1): 95-106


    The GTPase Ran has recently been shown to stimulate microtubule polymerization in mitotic extracts, but its mode of action is not understood. Here we show that the mitotic role of Ran is largely mediated by the nuclear transport factor importin beta. Importin beta inhibits spindle formation in vitro and in vivo and sequesters an aster promoting activity (APA) that consists of multiple, independent factors. One component of APA is the microtubule-associated protein NuMA. NuMA and other APA components are discharged from importin beta by RanGTP and induce spindle-like structures in the absence of centrosomes, chromatin, or Ran. We propose that RanGTP functions in mitosis as in interphase by locally releasing cargoes from transport factors. In mitosis, this promotes spindle assembly by organizing microtubules in the vicinity of chromosomes.

    View details for Web of Science ID 000166882300010

    View details for PubMedID 11163243

  • The direction of transport through the nuclear pore can be inverted PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Nachury, M. V., Weis, K. 1999; 96 (17): 9622-9627


    Transport of macromolecules across the nuclear envelope is an active process that depends on soluble factors including the GTPase Ran. Ran-GTP is predominantly located in the nucleus and has been shown to regulate cargo binding and release of import and export receptors in their respective target compartments. Recently, it was shown that transport of receptor-cargo complexes across the nuclear pore complex (NPC) does not depend on GTP-hydrolysis by Ran; however, the mechanism of translocation is still poorly understood. Here, we show that the direction of transport through the NPC can be inverted in the presence of high concentrations of cytoplasmic Ran-GTP. Under these conditions, two different classes of export cargoes are transported into the nucleus in the absence of GTP hydrolysis. The inverted transport is very rapid and can be blocked by known inhibitors of nuclear protein export. These results suggest that the NPC functions as a facilitated transport channel, allowing the selective translocation of receptor-cargo complexes. We conclude that the directionality of nucleocytoplasmic transport is determined mainly by the compartmentalized distribution of Ran-GTP.

    View details for Web of Science ID 000082098500034

    View details for PubMedID 10449743

  • Cloning and characterization of hSRP1 gamma, a tissue-specific nuclear transport factor PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Nachury, M. V., Ryder, U. W., Lamond, A. I., Weis, K. 1998; 95 (2): 582-587


    Nuclear import of proteins containing a nuclear localization signal (NLS) is dependent on the presence of a cytoplasmic NLS receptor, the GTPase Ran, and p10/ NTF2. The NLS receptor is a heterodimeric proteins consisting of subunits of approximately 60 and 97 kDa, which have been termed importin alpha/beta, karyopherin alpha/beta, or PTAC 58/ 97. Members of the 60-kDa/importin alpha subunit family directly bind to the NLS motif and have been shown to function as adaptors that tether NLS-containing proteins to the p97/ importin beta subunit and to the downstream transport machinery. Herein we report the identification and characterization of hSRP1 gamma, a human importin alpha homologue. The hSRP1 gamma protein is around 45% identical to the previously identified human importin alpha homologues hSRP1 alpha/Rch1 and NPI/ hSRP1. hSRP1 gamma can form a complex with importin beta and is able to mediate import of a BSA-NLS substrate in an in vitro nuclear import system. Interestingly, hSRP1 gamma shows a very selective expression pattern and is most abundantly expressed in skeletal muscle, representing more than 1% of the total protein in this tissue. A potential role for hSRP1 gamma in tissue-specific transport events is discussed.

    View details for Web of Science ID 000071606000028

    View details for PubMedID 9435235

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