Synaptic adhesion-like molecules (Homo sapiens)

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5, 7, 93, 461982, 4310cytosolGRIN2C Ca permeable AMPA receptors PTPRS L-Glu SALM3 SALM3 DLG3 SALMs 1-3:PSD-95familySALM3GRIN2C SALM2 SALM3:LAR-RPTPsAMPA, NMDA receptorsPSD-95 familySALM1 GRIN2A SALM1GRIN2B GRIN1 GRIN2B FLOT1 SALM1 GRIN2D PTPRD L-Glu PTPRF SALM2 SALM1 DLG4 GRIN2B GRIN2B GRIN2C GRIN1 GRIN2A DLG4 GRIN2C FLOT2 GRIN2A RTN3SALM4Ca permeable AMPA receptors SALM2,3(SALM1,4)SALM1 SALM2DLG3 PTPRF Gly NMDAR:PSD-95DLG1 SALM4:FLOT1(FLOT2)GRIN1 SALM2 SALM2:AMPA, NMDAreceptorsGRIN2A L-Glu SALM1,2,3SALM1:NMDAR:PSD-95RTN3 Gly Gly GRIN1 DLG1 SALM1 SALM3 SALM2 GRIN2D FLOT1(FLOT2)PTPRS L-Glu FLOT1 GRIN2D SALM1,2,3 dimerSALM4 SALM3 GRIN1 DLG4Gly Gly SALM2,3(SALM1,4):RTN3SALM4 DLG4 SALM1 PTPRF, PTPRS, PTPRDNMDA receptorcomplexGRIN2C GRIN2D SALM3 SALM2 SALM3 FLOT2 PTPRD L-Glu GRIN2A DLG4 GRIN2D GRIN2B SALM2 SALM4


Description

Recruitment of receptors and ion channels to the postsynaptic membrane is the last step in synapse formation. Many of these proteins interact directly or indirectly with postsynaptic density-95 (PSD95)/Discs large/zona occludens-1 (PDZ) proteins, thus linking them to the postsynaptic scaffold and providing a mechanism for both retaining the protein at the synapse and keeping its proximity to signaling molecules known to associate with PDZ proteins (Wang et al. 2006, Morimura et al. 2006, Ko et al. 2006, Nourry et al. 2003, Kim & Sheng 2004, Montgomery et al. 2004, Sheng and Kim 2011). The synaptic adhesion-like molecules (SALM) family belongs to the superfamily of leucine-rich repeat (LRR)-containing adhesion molecules, alternatively referred to as LRFN (leucine-rich repeat and fibronectin III domain-containing) is synapse adhesion molecule linked to NMDA and AMPA receptors. It includes five known members (SALMs 1-5 or LRFN1-5), which have been implicated in the regulation of neurite outgrowth and branching, and synapse formation and maturation. SALM proteins are distributed to both dendrites and axons in neurons (Ko et al. 2006, Wang et al. 2006, Sebold et al. 2012). The family members, SALM1-SALM5, have a single transmembrane (TM) domain and contain extracellular leucine-rich repeats, an Ig C2 type domain, a fibronectin type III domain, and an intracellular postsynaptic density-95 (PSD-95)/Discs large/zona occludens-1 (PDZ) binding domain, which is present on all members except SALM4 and SALM5 (Ko et al. 2006, Wang et al.2006, Morimura et al. 2006). View original pathway at:Reactome.

Comments

Reactome-Converter 
Pathway is converted from Reactome ID: 8849932
Reactome-version 
Reactome version: 66
Reactome Author 
Reactome Author: Garapati, Phani Vijay

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Bibliography

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  1. Swanwick CC, Shapiro ME, Vicini S, Wenthold RJ.; ''Flotillin-1 mediates neurite branching induced by synaptic adhesion-like molecule 4 in hippocampal neurons.''; PubMed Europe PMC
  2. Niethammer M, Kim E, Sheng M.; ''Interaction between the C terminus of NMDA receptor subunits and multiple members of the PSD-95 family of membrane-associated guanylate kinases.''; PubMed Europe PMC
  3. Wang CY, Chang K, Petralia RS, Wang YX, Seabold GK, Wenthold RJ.; ''A novel family of adhesion-like molecules that interacts with the NMDA receptor.''; PubMed Europe PMC
  4. Kornau HC, Schenker LT, Kennedy MB, Seeburg PH.; ''Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95.''; PubMed Europe PMC
  5. Nam J, Mah W, Kim E.; ''The SALM/Lrfn family of leucine-rich repeat-containing cell adhesion molecules.''; PubMed Europe PMC
  6. Chang K, Seabold GK, Wang CY, Wenthold RJ.; ''Reticulon 3 is an interacting partner of the SALM family of adhesion molecules.''; PubMed Europe PMC
  7. Sheng M, Kim E.; ''The postsynaptic organization of synapses.''; PubMed Europe PMC
  8. Li Y, Zhang P, Choi TY, Park SK, Park H, Lee EJ, Lee D, Roh JD, Mah W, Kim R, Kim Y, Kwon H, Bae YC, Choi SY, Craig AM, Kim E.; ''Splicing-Dependent Trans-synaptic SALM3-LAR-RPTP Interactions Regulate Excitatory Synapse Development and Locomotion.''; PubMed Europe PMC
  9. Ko J, Kim S, Chung HS, Kim K, Han K, Kim H, Jun H, Kaang BK, Kim E.; ''SALM synaptic cell adhesion-like molecules regulate the differentiation of excitatory synapses.''; PubMed Europe PMC
  10. Seabold GK, Wang PY, Chang K, Wang CY, Wang YX, Petralia RS, Wenthold RJ.; ''The SALM family of adhesion-like molecules forms heteromeric and homomeric complexes.''; PubMed Europe PMC

History

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CompareRevisionActionTimeUserComment
101244view11:13, 1 November 2018ReactomeTeamreactome version 66
100783view20:40, 31 October 2018ReactomeTeamreactome version 65
100325view19:17, 31 October 2018ReactomeTeamreactome version 64
99870view16:00, 31 October 2018ReactomeTeamreactome version 63
99427view14:36, 31 October 2018ReactomeTeamreactome version 62 (2nd attempt)
93327view11:20, 9 August 2017ReactomeTeamNew pathway

External references

DataNodes

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NameTypeDatabase referenceComment
AMPA, NMDA receptorsComplexR-HSA-8849876 (Reactome)
Ca permeable AMPA receptors R-HSA-399714 (Reactome)
DLG1 ProteinQ12959 (Uniprot-TrEMBL)
DLG3 ProteinQ92796 (Uniprot-TrEMBL)
DLG4 ProteinP78352 (Uniprot-TrEMBL)
DLG4ProteinP78352 (Uniprot-TrEMBL)
FLOT1 ProteinO75955 (Uniprot-TrEMBL)
FLOT1(FLOT2)ComplexR-HSA-8849894 (Reactome)
FLOT2 ProteinQ14254 (Uniprot-TrEMBL)
GRIN1 ProteinQ05586 (Uniprot-TrEMBL)
GRIN2A ProteinQ12879 (Uniprot-TrEMBL)
GRIN2B ProteinQ13224 (Uniprot-TrEMBL)
GRIN2C ProteinQ14957 (Uniprot-TrEMBL)
GRIN2D ProteinO15399 (Uniprot-TrEMBL)
Gly MetaboliteCHEBI:57305 (ChEBI)
L-Glu MetaboliteCHEBI:29985 (ChEBI)
NMDA receptor complexComplexR-HSA-8849905 (Reactome)
NMDAR:PSD-95ComplexR-HSA-8849869 (Reactome)
PSD-95 familyComplexR-HSA-376003 (Reactome)
PTPRD ProteinP23468 (Uniprot-TrEMBL)
PTPRF ProteinP10586 (Uniprot-TrEMBL)
PTPRF, PTPRS, PTPRDComplexR-HSA-6798238 (Reactome)
PTPRS ProteinQ13332 (Uniprot-TrEMBL)
RTN3 ProteinO95197 (Uniprot-TrEMBL)
RTN3ProteinO95197 (Uniprot-TrEMBL)
SALM1 ProteinQ9ULH4 (Uniprot-TrEMBL)
SALM1,2,3 dimerComplexR-HSA-8849910 (Reactome)
SALM1,2,3ComplexR-HSA-204742 (Reactome)
SALM1:NMDAR:PSD-95ComplexR-HSA-8849935 (Reactome)
SALM1ProteinQ9ULH4 (Uniprot-TrEMBL)
SALM2 ProteinQ9P244 (Uniprot-TrEMBL)
SALM2,3(SALM1,4):RTN3ComplexR-HSA-8849893 (Reactome)
SALM2,3(SALM1,4)ComplexR-HSA-8849896 (Reactome)
SALM2:AMPA, NMDA receptorsComplexR-HSA-8849914 (Reactome)
SALM2ProteinQ9P244 (Uniprot-TrEMBL)
SALM3 ProteinQ6PJG9 (Uniprot-TrEMBL)
SALM3:LAR-RPTPsComplexR-HSA-8855645 (Reactome)
SALM3ProteinQ6PJG9 (Uniprot-TrEMBL)
SALM4 ProteinQ9BTN0 (Uniprot-TrEMBL)
SALM4:FLOT1(FLOT2)ComplexR-HSA-8849870 (Reactome)
SALM4ProteinQ9BTN0 (Uniprot-TrEMBL)
SALMs 1-3:PSD-95 familyComplexR-HSA-8849913 (Reactome)

Annotated Interactions

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SourceTargetTypeDatabase referenceComment
AMPA, NMDA receptorsR-HSA-8849881 (Reactome)
DLG4R-HSA-8849878 (Reactome)
FLOT1(FLOT2)R-HSA-8849908 (Reactome)
NMDA receptor complexR-HSA-8849878 (Reactome)
NMDAR:PSD-95ArrowR-HSA-8849878 (Reactome)
NMDAR:PSD-95R-HSA-8849906 (Reactome)
PSD-95 familyR-HSA-8849891 (Reactome)
PTPRF, PTPRS, PTPRDR-HSA-8855648 (Reactome)
R-HSA-8849878 (Reactome) Many membrane proteins that contain a PDZ-binding domain require an interaction with a PDZ protein for correct targeting to the cell surface (Zheng et al. 2011). N-methyl-D-aspartate (NMDA) receptor interact with postsynaptic density protein (PSD-95) and the PSD-95 family might serve to anchor NMDA receptors to the submembrane cytoskeleton and aid in the assembly of signal transduction complexes at postsynaptic sites (Niethammer et al. 1996, Kornau et al. 1995, Sans et al. 2000).
R-HSA-8849881 (Reactome) SALM2 coimmunoprecipitates with NMDAR and AMPAR subunits isolated from detergent-solubilized brain (Ko et al. 2006). SALM2 co localizes with both pre- and post-synaptic proteins at excitatory synapses in mature neurons. SALM2 associates with AMPA receptors and, to a lesser extent, with NMDA receptors in hippocampal cultures. SALM2 appears to promote the maturation, but not the formation, of excitatory synapses, in line with the fact that synaptic localization of AMPA receptors occurs at late stages of excitatory synaptic development (Ko et al. 2006, Nam et al. 2011).
R-HSA-8849882 (Reactome) In the brain, reticulon 3 (RTN3) tightly associates with SALM2 and SALM3 to form a complex, and interacts relatively weakly with SALM1 and SALM4. This interaction is mediated by the LRR domain in SALMs (Chang et al. 2010).
R-HSA-8849891 (Reactome) SALMs 1-3 interact with the PDZ domain containing proteins PSD 95 (DLG4) and synapse associated protein 97 (SAP97 or DLG1) and SAP102 (DLG3), based on yeast 2-hybrid assays (Wang et al. 2006, Ko et al. 2006) and coimmunoprecipitations from detergent solubilized brain (Wang et al. 2006, Ko et al. 2006, Mah et al. 2010) and transiently transfected mammalian cells (Morimura et al., 2006, Wang et al. 2006). PDZ proteins play a central role in organizing functionally diverse membrane proteins at the synapse (Wang et al. 2006, Zheng et al. 2011). PSD-95 family members are abundant postsynaptic scaffolding proteins at excitatory synapses. SALM1 (Wang et al. 2006), SALM2 (Ko et al. 2006), SALM3 and SALM5 (Mah et al. 2010) proteins are enriched in synaptic fractions. SALM5 forms a weak complex with PSD-95, an abundant postsynaptic scaffolding protein at excitatory synapse most likely through indirect interactions (Mah et al. 2010). SALM3 and SALM5, but not other SALMs, induce presynaptic differentiation in contacting axons (Mah et al. 2010).
R-HSA-8849900 (Reactome) SALM1, SALM2, and SALM3 form homo- and heteromeric complexes in a cis manner. These SALMs 1-3 coimmunoprecipitate with each other in extracts from brain. Whether the homo and heteromeric complexes formed between SALMs 1-3 contribute to synapse formation or neurite outgrowth remains to be determined (Seabold et al. 2008).
R-HSA-8849906 (Reactome) SALM1 interacts with and recruits NMDA receptors to early synapses. NMDA receptors are involved in the development of excitatory synapse by interacting with PDZ proteins of the PSD-95 family through its NR2 subunits. SALM1 can directly interact with the extracellular domain of the NR1 subunit of NMDA receptor or indirectly by binding to PSD-95, which may recruit NMDA receptor via the NR2 subunits of NMDA receptors (Wang et al. 2006, Niethammer et al. 1996, Kornau et al. 1995). SALM1 also often localizes with the NR1 subunit of NMDA receptors in hippocampal and cerebellar neurons (Thevenon et al., 2015).
R-HSA-8849908 (Reactome) SALM4 induces neurite branching by binding to flotillin-1, a lipid raft-associated protein that interacts with NMDA receptors (Swanwick et al. 2009, 2010).
R-HSA-8855648 (Reactome) SALM3 interacts with LAR family receptor protein tyrosine phosphatases (LAR-RPTPs) in a transynaptic manner that is dependent upon a splice insert in LAR-RPTPs. This interaction regulates SALM3 dependent presynaptic differentiation (Li et al. 2015). SALM3 knockout mice have fewer excitatory synapsese, but normal plasticity in the hippocampus. However, they are hypoactive, suggesting SALM3 influences locomotion behavior (Li et al. 2015).
RTN3R-HSA-8849882 (Reactome)
SALM1,2,3 dimerArrowR-HSA-8849900 (Reactome)
SALM1,2,3R-HSA-8849891 (Reactome)
SALM1,2,3R-HSA-8849900 (Reactome)
SALM1:NMDAR:PSD-95ArrowR-HSA-8849906 (Reactome)
SALM1R-HSA-8849906 (Reactome)
SALM2,3(SALM1,4):RTN3ArrowR-HSA-8849882 (Reactome)
SALM2,3(SALM1,4)R-HSA-8849882 (Reactome)
SALM2:AMPA, NMDA receptorsArrowR-HSA-8849881 (Reactome)
SALM2R-HSA-8849881 (Reactome)
SALM3:LAR-RPTPsArrowR-HSA-8855648 (Reactome)
SALM3R-HSA-8855648 (Reactome)
SALM4:FLOT1(FLOT2)ArrowR-HSA-8849908 (Reactome)
SALM4R-HSA-8849908 (Reactome)
SALMs 1-3:PSD-95 familyArrowR-HSA-8849891 (Reactome)
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