1va8

Structural highlights

Function

PALS1_MOUSE Plays a role in tight junction biogenesis and in the establishment of cell polarity in epithelial cells (By similarity). Also involved in adherens junction biogenesis by ensuring correct localization of the exocyst complex protein EXOC4/SEC8 which allows trafficking of adherens junction structural component CDH1 to the cell surface (PubMed:17182851, PubMed:20237282). Plays a role through its interaction with CDH5 in vascular lumen formation and endothelial membrane polarity (By similarity). Required during embryonic and postnatal retinal development (PubMed:22398208). Required for the maintenance of cerebellar progenitor cells in an undifferentiated proliferative state, preventing premature differentiation, and is required for cerebellar histogenesis, fissure formation, cerebellar layer organization and cortical development (PubMed:20399730, PubMed:26404741). Plays a role in neuronal progenitor cell survival, potentially via promotion of mTOR signaling (PubMed:20399730). Plays a role in the radial and longitudinal extension of the myelin sheath in Schwann cells (PubMed:20237282). May modulate SC6A1/GAT1-mediated GABA uptake by stabilizing the transporter (PubMed:15234345). May play a role in the T-cell receptor-mediated activation of NF-kappa-B (By similarity). Required for localization of EZR to the apical membrane of parietal cells and may play a role in the dynamic remodeling of the apical cytoskeleton (PubMed:15677456). Required for the normal polarized localization of the vesicular marker STX4 (PubMed:20237282). Required for the correct trafficking of the myelin proteins PMP22 and MAG (By similarity). Involved in promoting phosphorylation and cytoplasmic retention of transcriptional coactivators YAP1 and WWTR1/TAZ which leads to suppression of TGFB1-dependent transcription of target genes such as CCN2/CTGF, SERPINE1/PAI1, SNAI1/SNAIL1 and SMAD7 (PubMed:21145499).[UniProtKB:B4F7E7][UniProtKB:Q8N3R9]^{[1] [2] [3] [4] [5] [6] [7] [8] [9]}

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

References

1. ↑ McHugh EM, Zhu W, Milgram S, Mager S. The GABA transporter GAT1 and the MAGUK protein Pals1: interaction, uptake modulation, and coexpression in the brain. Mol Cell Neurosci. 2004 Jul;26(3):406-17. PMID:15234345 doi:10.1016/j.mcn.2004.03.006
2. ↑ Cao X, Ding X, Guo Z, Zhou R, Wang F, Long F, Wu F, Bi F, Wang Q, Fan D, Forte JG, Teng M, Yao X. PALS1 specifies the localization of ezrin to the apical membrane of gastric parietal cells. J Biol Chem. 2005 Apr 8;280(14):13584-92. Epub 2005 Jan 27. PMID:15677456 doi:http://dx.doi.org/10.1074/jbc.M411941200
3. ↑ Wang Q, Chen XW, Margolis B. PALS1 regulates E-cadherin trafficking in mammalian epithelial cells. Mol Biol Cell. 2007 Mar;18(3):874-85. PMID:17182851 doi:10.1091/mbc.e06-07-0651
4. ↑ Ozçelik M, Cotter L, Jacob C, Pereira JA, Relvas JB, Suter U, Tricaud N. Pals1 is a major regulator of the epithelial-like polarization and the extension of the myelin sheath in peripheral nerves. J Neurosci. 2010 Mar 17;30(11):4120-31. PMID:20237282 doi:10.1523/JNEUROSCI.5185-09.2010
5. ↑ Kim S, Lehtinen MK, Sessa A, Zappaterra MW, Cho SH, Gonzalez D, Boggan B, Austin CA, Wijnholds J, Gambello MJ, Malicki J, LaMantia AS, Broccoli V, Walsh CA. The apical complex couples cell fate and cell survival to cerebral cortical development. Neuron. 2010 Apr 15;66(1):69-84. PMID:20399730 doi:10.1016/j.neuron.2010.03.019
6. ↑ Varelas X, Samavarchi-Tehrani P, Narimatsu M, Weiss A, Cockburn K, Larsen BG, Rossant J, Wrana JL. The Crumbs complex couples cell density sensing to Hippo-dependent control of the TGF-β-SMAD pathway. Dev Cell. 2010 Dec 14;19(6):831-44. PMID:21145499 doi:10.1016/j.devcel.2010.11.012
7. ↑ Cho SH, Kim JY, Simons DL, Song JY, Le JH, Swindell EC, Jamrich M, Wu SM, Kim S. Genetic ablation of Pals1 in retinal progenitor cells models the retinal pathology of Leber congenital amaurosis. Hum Mol Genet. 2012 Jun 15;21(12):2663-76. PMID:22398208 doi:10.1093/hmg/dds091
8. ↑ Paniagua AE, Herranz-Martín S, Jimeno D, Jimeno ÁM, López-Benito S, Carlos Arévalo J, Velasco A, Aijón J, Lillo C. CRB2 completes a fully expressed Crumbs complex in the Retinal Pigment Epithelium. Sci Rep. 2015 Sep 25;5:14504. PMID:26404741 doi:10.1038/srep14504
9. ↑ Park JY, Hughes LJ, Moon UY, Park R, Kim SB, Tran K, Lee JS, Cho SH, Kim S. The apical complex protein Pals1 is required to maintain cerebellar progenitor cells in a proliferative state. Development. 2016 Jan 1;143(1):133-46. PMID:26657772 doi:10.1242/dev.124180