| Structural highlights
Disease
[SLIK1_HUMAN] Tourette syndrome. The disease may be caused by mutations affecting the gene represented in this entry. The disease may be caused by mutations affecting the gene represented in this entry.
Function
[SLIK1_HUMAN] Enhances neuronal dendrite outgrowth.[1]
Publication Abstract from PubMed
Synaptic adhesion molecules orchestrate synaptogenesis. The presynaptic leukocyte common antigen-related receptor protein tyrosine phosphatases (LAR-RPTPs) regulate synapse development by interacting with postsynaptic Slit- and Trk-like family proteins (Slitrks), which harbour two extracellular leucine-rich repeats (LRR1 and LRR2). Here we identify the minimal regions of the LAR-RPTPs and Slitrks, LAR-RPTPs Ig1-3 and Slitrks LRR1, for their interaction and synaptogenic function. Subsequent crystallographic and structure-guided functional analyses reveal that the splicing inserts in LAR-RPTPs are key molecular determinants for Slitrk binding and synapse formation. Moreover, structural comparison of the two Slitrk1 LRRs reveal that unique properties on the concave surface of Slitrk1 LRR1 render its specific binding to LAR-RPTPs. Finally, we demonstrate that lateral interactions between adjacent trans-synaptic LAR-RPTPs/Slitrks complexes observed in crystal lattices are critical for Slitrk1-induced lateral assembly and synaptogenic activity. Thus, we propose a model in which Slitrks mediate synaptogenic functions through direct binding to LAR-RPTPs and the subsequent lateral assembly of LAR-RPTPs/Slitrks complexes.
Structural basis for LAR-RPTP/Slitrk complex-mediated synaptic adhesion.,Um JW, Kim KH, Park BS, Choi Y, Kim D, Kim CY, Kim SJ, Kim M, Ko JS, Lee SG, Choii G, Nam J, Heo WD, Kim E, Lee JO, Ko J, Kim HM Nat Commun. 2014 Nov 14;5:5423. doi: 10.1038/ncomms6423. PMID:25394468[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Abelson JF, Kwan KY, O'Roak BJ, Baek DY, Stillman AA, Morgan TM, Mathews CA, Pauls DL, Rasin MR, Gunel M, Davis NR, Ercan-Sencicek AG, Guez DH, Spertus JA, Leckman JF, Dure LS 4th, Kurlan R, Singer HS, Gilbert DL, Farhi A, Louvi A, Lifton RP, Sestan N, State MW. Sequence variants in SLITRK1 are associated with Tourette's syndrome. Science. 2005 Oct 14;310(5746):317-20. PMID:16224024 doi:http://dx.doi.org/10.1126/science.1116502
- ↑ Um JW, Kim KH, Park BS, Choi Y, Kim D, Kim CY, Kim SJ, Kim M, Ko JS, Lee SG, Choii G, Nam J, Heo WD, Kim E, Lee JO, Ko J, Kim HM. Structural basis for LAR-RPTP/Slitrk complex-mediated synaptic adhesion. Nat Commun. 2014 Nov 14;5:5423. doi: 10.1038/ncomms6423. PMID:25394468 doi:http://dx.doi.org/10.1038/ncomms6423
|
