TY - JOUR
T1 - Ptpσ functions as a presynaptic receptor for the glypican-4/LRRTM4 complex and is essential for excitatory synaptic transmission
AU - Ji, Seung Ko
AU - Gopal, Pramanikb
AU - Ji, Won Uma
AU - Ji, Seon Shimd
AU - Dongmin, Leee
AU - Kee, Hun Kimf
AU - Gug-Young, Chunga
AU - Giuseppe, Condomittig
AU - Ho, Min Kimf
AU - Hyun, Kim
AU - De Joris, Wit
AU - Kang-Sik, Park
AU - Katsuhiko, Tabuchi
AU - Jaewon, Ko
PY - 2015/2/10
Y1 - 2015/2/10
N2 - Leukocyte common antigen-related receptor protein tyrosine phosphatases-comprising LAR, PTPaδ, and PTPoσ-are synaptic adhesion molecules that organize synapse development. Here, we identify glypican 4 (GPC-4) as a ligand for PTPσ GPC-4 showed strong (nanomolar) affinity and heparan sulfate (HS)-dependent interaction with the Ig domains of PTPσPTPσ 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 PTPσ 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, PTPσ KD dramatically decreased both the frequency and amplitude of excitatory synaptic transmission. This effect was reversed by wild-type PTPoσ but not by a HS-binding-defective PTPσ mutant. Our results collectively suggest that presynaptic PTPσ together with GPC-4, acts in a HS-dependent manner to maintain excitatory synapse development and function. PTPσglypicanLRRTM4 synaptic cell adhesionheparan sulfate.
AB - Leukocyte common antigen-related receptor protein tyrosine phosphatases-comprising LAR, PTPaδ, and PTPoσ-are synaptic adhesion molecules that organize synapse development. Here, we identify glypican 4 (GPC-4) as a ligand for PTPσ GPC-4 showed strong (nanomolar) affinity and heparan sulfate (HS)-dependent interaction with the Ig domains of PTPσPTPσ 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 PTPσ 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, PTPσ KD dramatically decreased both the frequency and amplitude of excitatory synaptic transmission. This effect was reversed by wild-type PTPoσ but not by a HS-binding-defective PTPσ mutant. Our results collectively suggest that presynaptic PTPσ together with GPC-4, acts in a HS-dependent manner to maintain excitatory synapse development and function. PTPσglypicanLRRTM4 synaptic cell adhesionheparan sulfate.
UR - http://www.scopus.com/inward/record.url?scp=84922624895&partnerID=8YFLogxK
U2 - 10.1073/pnas.1410138112
DO - 10.1073/pnas.1410138112
M3 - Article
C2 - 25624497
AN - SCOPUS:84922624895
SN - 0027-8424
VL - 112
SP - 1874
EP - 1879
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 6
ER -