CDB25:0003933 LRRTM4 — PTPRS

Experimentally validated in Rat; Orthology-inferred in Human, Mouse, Frog, Zebrafish, Chicken, Macaque, Pig, Dog, Cow, Chimp, Horse, Marmoset, Sheep

Title

Journal:; Year Published:

Abstract

PTPσ 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, 2015; PubMed, Rattus norvegicus Lrrtm4 — Rattus norvegicus Ptprs

ABSTRACT: Leukocyte common antigen-related receptor protein tyrosine phosphatases--comprising LAR, PTPδ, and PTPσ--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 PTPσ. PTPσ 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 PTPσ, 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.

Basic Information on LRRTM4

Ligand Name: leucine rich repeat transmembrane neuronal 4

Other Symbols: FLJ12568

Ligand Location: cell membrane based on perplexity, uniprot

HGNC Gene Symbol Report: LRRTM4

GeneCards: LRRTM4

HGNC Gene Group: unknown

Functional Annotations for LRRTM4

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Receptors for LRRTM4

LRRTM4 — GPC1 ・ LRRTM4 — GPC3 ・ LRRTM4 — GPC4 ・ LRRTM4 — GPC5 ・ LRRTM4 — GPC6 ・ LRRTM4 — NRXN1

Basic Information on PTPRS

Receptor Name: protein tyrosine phosphatase receptor type S

Other Symbols: PTPsigma, PTP-sigma

Receptor Location: cell membrane based on hpa, perplexity, uniprot

HGNC Gene Symbol Report: PTPRS

GeneCards: PTPRS

HGNC Gene Group: Phosphatases, LAR (PTPRF) protein receptor tyrosine phosphatase family, Fibronectin type III domain containing, Immunoglobulin superfamily domain containing

Functional Annotations for PTPRS

Gene Ontologies: PAN-GO, AmiGO 2

Expression Profile: Human Protein Atlas (RNA and protein), Human Cell Atlas (RNA), GEPIA cancer vs normal (RNA), GeneCards (RNA and protein)

Disease Annotations: MalaCards, OMIM, Open Targets Platform, DISEASES (text mining), AI summary (LLM)

Interactions with other Ligands for PTPRS

COL18A1 — PTPRS ・ LRRC4B — PTPRS ・ NTRK3 — PTPRS ・ SLITRK1 — PTPRS ・ SLITRK2 — PTPRS ・ SLITRK3 — PTPRS ・ SLITRK6 — PTPRS ・ AGRN — PTPRS ・ GPC4 — PTPRS ・ LRFN4 — PTPRS ・ LRFN5 — PTPRS ・ OMG — PTPRS