1.A.1.11.36 Two pore segment channel 1 of 790 aas and 12 TMSs in a 3 + 3 (N-terminal half) + 2 + 2 + 2 (C-terminal half) TMS arrangement. In the trunk of developing zebrafish embryos, adjacent myotome blocks transmit contractile force via myoseptal junctions (MJs), dynamic structures that connect the actin cytoskeleton of skeletal muscle cells to extracellular matrix components via transmembrane protein complexes in the sarcolemma. Rice et al. 2022 reported that the endolysosomal ion channel, TPC1, generates highly localized, non-propagating Ca2+ transients that play a distinct and required role in the capture and attachment of superficial slow skeletal muscle cells (SMCs) at MJs. Disruption of the tpcn1 gene resulted in abnormal MJ phenotypes including SMCs detaching from or crossing the myosepta. TPC1-decorated endolysosomes are dynamically associated with MJs in a microtubule-dependent manner, and attenuating tpcn1 expression or function disrupted endolysosomal trafficking and resulted in an abnormal distribution of beta-dystroglycan (a key transmembrane component of the dystrophin-associated protein complex). Thus, localized TPC1-generated Ca2+ signals facilitate essential endolysosomal trafficking and membrane contact events, which help form and maintain MJs following the onset of SMC contractile activity (Rice et al. 2022).
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Accession Number: | F1R4Z3 |
Protein Name: | Two pore segment channel 1 |
Length: | 790 |
Molecular Weight: | 91657.00 |
Species: | Danio rerio (Zebrafish) [7955] |
Number of TMSs: | 12 |
Substrate |
calcium(2+) |
---|
1: MKNHLIFFFL LYTDGAGNHD VVNNVTIPAS GASDPRAQNS LQQSWEMNFQ EAAIYLQEGE
61: NNDKFFTHPR SAHALSAYLF AHSHLFYVVE LLTAVLLMLL SLSEAPAVPF LRLDVYVHAT
121: LELLALVMVA FELCMKLRWL GFHTFIRHKR TMVKTSVLFI QFIEAIVVLV RQTSHLRVTR
181: ALRPIFLVDC RYCGAVRRNL RQIFQSLPPF IDILLLLLFF MVIFAILGFC LFSANTADHY
241: FSTLENSIVS LFVLLTTANF PDVMMPAYSK NRWSCIFFIV YLSIELYFIM NLLLAVVFDT
301: FNGVEKMKFK SLLLHKRSAI EHAFQLLVSR QRPDGVSLKQ FDGLMRFYHP RMTPRDRFLT
361: FKALNHSGAP MLSLQDFYKF YEVIGLKWKA RRSGEHWFDD LPRTALLIFK DLVVAVNGIW
421: ILVETNMLNG FHSNINFFII IIYLLFMFRW NEVYGIEVLL KITGLGPITY FSSGWNLFDF
481: SVTVFAFLGL IALAFDMEPF YFIVVLRPLQ LLRLFKIKQR YRNVLDTMFE LFPRMASLGL
541: TLIIFYYSFA IVGMEFFADV IYPNCCDNST VAASYRQINV TTGNRTELQE GYYYLNNFNN
601: ILSSFVTLFE LTVVNNWYIT MEGVTSQTTH WSRLYFMTFY IVTMVVMTII VAFILDAFVF
661: RMNYSRKNRE PVTGTFFTEI SNTESLCGIV FETEVSQTEA LQTLDFYKHT LGVTNLTSLQ
721: DMCVALERSG QTSLVFLGRR SRTKSDLSMK MYEEEIQEWY EEYSRTNLQT DGTFHRELDS
781: PDAGATNSIN