期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2015
卷号：112
期号：6
页码：1874-1879
DOI：10.1073/pnas.1410138112
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：SignificanceThis paper documents and systematically characterizes the molecular interactions of protein tyrosine phosphatase {sigma} (PTP{sigma}) with glypicans (GPCs). The identified interactions require heparan sulfate (HS), suggesting that GPCs are a major source of HS for PTP{sigma} at excitatory synapses. Strikingly, we found that leucine-rich repeat transmembrane protein 4 (LRRTM4) induces presynaptic differentiation via the PTP{sigma}/GPC interaction, suggesting that PTP{sigma} may function as a coreceptor for GPCs in presynaptic neurons. More importantly, we found that HS-binding ability of PTP{sigma} is critical for excitatory synaptic transmission. These results expand our previous understanding of how synaptic adhesion pathways regulate excitatory synapse development and shed light on GPCs/LRRTM4 trans-synaptic signaling. Moreover, to our knowledge, this is the first study to document the physiological significance of HS in the presynaptic function of mammalian neurons. Leukocyte common antigen-related receptor protein tyrosine phosphatases--comprising LAR, PTP{delta
