Latest information on COVID-19

Stanford Medicine is closely monitoring the COVID-19 pandemic. Get the latest news on COVID-19 testing, treatment, tracking data, and medical research.

Racism and discrimination are direct affronts to Stanford Medicine?s values. Read our leaders? pledge on racial equity.

A leader in the biomedical revolution, Stanford Medicine has a long tradition of leadership in pioneering research, creative teaching protocols and effective clinical therapies.

Analyzing a national cancer database, Stanford Medicine researchers find a bump in diagnoses at 65, suggesting that many wait for Medicare to kick in before they seek care.

Our scientists have launched dozens of research projects as part of the global response to COVID-19. Some aim to prevent, diagnose and treat the disease; others aim to understand how it spreads and how people?s immune systems respond to it.

A Stanford Medicine team offered guidance in crafting a COVID-19 response for the Oglala Lakota Nation.

Medical students recently learned where they would be heading for their residencies.

Sharon Hampton is focusing on patient equity as a nursing leader at Stanford Health Care. Getting to know patients and staff is key, she says.

Bio

Institute Affiliations


  • Member, Maternal & Child Health Research Institute (MCHRI)

Professional Education


  • Master of Technology, Indian Institute of Technology, Kharagpur (2005)
  • Bachelor of Technology, Jadavpur University (2002)
  • Doctor of Philosophy, Sokendai Graduate University for Advanced Studies (2015)

Publications

All Publications


  • PTP? Drives Excitatory Presynaptic Assembly via Various Extracellular and Intracellular Mechanisms. The Journal of neuroscience : the official journal of the Society for Neuroscience Han, K. A., Ko, J. S., Pramanik, G. n., Kim, J. Y., Tabuchi, K. n., Um, J. W., Ko, J. n. 2018; 38 (30): 6700?6721

    Abstract

    Leukocyte common antigen-receptor protein tyrosine phosphatases (LAR-RPTPs) are hub proteins that organize excitatory and inhibitory synapse development through binding to various extracellular ligands. Here, we report that knockdown (KD) of the LAR-RPTP family member PTP? reduced excitatory synapse number and transmission in cultured rat hippocampal neurons, whereas KD of PTP? produced comparable decreases at inhibitory synapses, in both cases without altering expression levels of interacting proteins. An extensive series of rescue experiments revealed that extracellular interactions of PTP? with Slitrks are important for excitatory synapse development. These experiments further showed that the intracellular D2 domain of PTP? is required for induction of heterologous synapse formation by Slitrk1 or TrkC, suggesting that interaction of LAR-RPTPs with distinct intracellular presynaptic proteins, drives presynaptic machinery assembly. Consistent with this, double-KD of liprin-?2 and -?3 or KD of PTP? substrates (N-cadherin and p250RhoGAP) in neurons inhibited Slitrk6-induced, PTP?-mediated heterologous synapse formation activity. We propose a synaptogenesis model in presynaptic neurons involving LAR-RPTP-organized retrograde signaling cascades, in which both extracellular and intracellular mechanisms are critical in orchestrating distinct synapse types.SIGNIFICANCE STATEMENT In this study, we sought to test the unproven hypothesis that PTP? and PTP? are required for excitatory and inhibitory synapse formation/transmission, respectively, in cultured hippocampal neurons, using knockdown-based loss-of-function analyses. We further performed extensive structure-function analyses, focusing on PTP?-mediated actions, to address the mechanisms of presynaptic assembly at excitatory synaptic sites. Using interdisciplinary approaches, we systematically applied a varied set of PTP? deletion variants, point mutants, and splice variants to demonstrate that both extracellular and intracellular mechanisms are involved in organizing presynaptic assembly. Strikingly, extracellular interactions of PTP? with heparan sulfates and Slitrks, intracellular interactions of PTP? with liprin-? and its associated proteins through the D2 domain, as well as distinct substrates are all critical.

    View details for DOI 10.1523/JNEUROSCI.0672-18.2018

    View details for PubMedID 29934346

  • PTP sigma functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic transmission PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Ko, J. S., Pramanik, G., Um, J. W., Shim, J. S., Lee, D., Kim, K. H., Chung, G., Condomitti, G., Kim, H. M., Kim, H., de Wit, J., Park, K., Tabuchi, K., Ko, J. 2015; 112 (6): 1874-1879

    Abstract

    Leukocyte common antigen-related receptor protein tyrosine phosphatases--comprising LAR, PTP?, and PTP?--are synaptic adhesion molecules that organize synapse development. Here, we identify glypican 4 (GPC-4) as a ligand for PTP?. GPC-4 showed strong (nanomolar) affinity and heparan sulfate (HS)-dependent interaction with the Ig domains of PTP?. PTP? bound only to proteolytically cleaved GPC-4 and formed additional complex with leucine-rich repeat transmembrane protein 4 (LRRTM4) in rat brains. Moreover, single knockdown (KD) of PTP?, but not LAR, in cultured neurons significantly reduced the synaptogenic activity of LRRTM4, a postsynaptic ligand of GPC-4, in heterologous synapse-formation assays. Finally, PTP? KD dramatically decreased both the frequency and amplitude of excitatory synaptic transmission. This effect was reversed by wild-type PTP?, but not by a HS-binding-defective PTP? mutant. Our results collectively suggest that presynaptic PTP?, together with GPC-4, acts in a HS-dependent manner to maintain excitatory synapse development and function.

    View details for DOI 10.1073/pnas.1410138112

    View details for Web of Science ID 000349204200062

    View details for PubMedID 25624497

  • Calsyntenins function as synaptogenic adhesion molecules in concert with neurexins. Cell reports Um, J. W., Pramanik, G., Ko, J. S., Song, M., Lee, D., Kim, H., Park, K., Südhof, T. C., Tabuchi, K., Ko, J. 2014; 6 (6): 1096-1109

    Abstract

    Multiple synaptic adhesion molecules govern synapse formation. Here, we propose calsyntenin-3/alcadein-? as a synapse organizer that specifically induces presynaptic differentiation in heterologous synapse-formation assays. Calsyntenin-3 (CST-3) is highly expressed during various postnatal periods of mouse brain development. The simultaneous knockdown of all three CSTs, but not CST-3 alone, decreases inhibitory, but not excitatory, synapse densities in cultured hippocampal neurons. Moreover, the knockdown of CSTs specifically reduces inhibitory synaptic transmission in vitro and in vivo. Remarkably, the loss of CSTs induces a concomitant decrease in neuron soma size in a non-cell-autonomous manner. Furthermore, ?-neurexins (?-Nrxs) are components of a CST-3 complex involved in CST-3-mediated presynaptic differentiation. However, CST-3 does not directly bind to Nrxs. Viewed together, these data suggest that the three CSTs redundantly regulate inhibitory synapse formation, inhibitory synapse function, and neuron development in concert with Nrxs.

    View details for DOI 10.1016/j.celrep.2014.02.010

    View details for PubMedID 24613359

Home | Stanford Medicine

Latest information on COVID-19

Stanford Medicine is closely monitoring the COVID-19 pandemic. Get the latest news on COVID-19 testing, treatment, tracking data, and medical research.

Racism and discrimination are direct affronts to Stanford Medicine?s values. Read our leaders? pledge on racial equity.

A leader in the biomedical revolution, Stanford Medicine has a long tradition of leadership in pioneering research, creative teaching protocols and effective clinical therapies.

Analyzing a national cancer database, Stanford Medicine researchers find a bump in diagnoses at 65, suggesting that many wait for Medicare to kick in before they seek care.

Our scientists have launched dozens of research projects as part of the global response to COVID-19. Some aim to prevent, diagnose and treat the disease; others aim to understand how it spreads and how people?s immune systems respond to it.

A Stanford Medicine team offered guidance in crafting a COVID-19 response for the Oglala Lakota Nation.

Medical students recently learned where they would be heading for their residencies.

Sharon Hampton is focusing on patient equity as a nursing leader at Stanford Health Care. Getting to know patients and staff is key, she says.

Home | Stanford Medicine

Latest information on COVID-19

Stanford Medicine is closely monitoring the COVID-19 pandemic. Get the latest news on COVID-19 testing, treatment, tracking data, and medical research.

Racism and discrimination are direct affronts to Stanford Medicine?s values. Read our leaders? pledge on racial equity.

A leader in the biomedical revolution, Stanford Medicine has a long tradition of leadership in pioneering research, creative teaching protocols and effective clinical therapies.

Analyzing a national cancer database, Stanford Medicine researchers find a bump in diagnoses at 65, suggesting that many wait for Medicare to kick in before they seek care.

Our scientists have launched dozens of research projects as part of the global response to COVID-19. Some aim to prevent, diagnose and treat the disease; others aim to understand how it spreads and how people?s immune systems respond to it.

A Stanford Medicine team offered guidance in crafting a COVID-19 response for the Oglala Lakota Nation.

Medical students recently learned where they would be heading for their residencies.

Sharon Hampton is focusing on patient equity as a nursing leader at Stanford Health Care. Getting to know patients and staff is key, she says.

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