Septin-microtubule association via a motif unique to isoform 1 of septin 9 tunes stress fibers
Septin-microtubule association via a motif unique to isoform 1 of septin 9 tunes stress fibers
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DOI：
10.1242/jcs.258850
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发表时间：
2022-01-01
影响因子：
4
通讯作者：
Verdier-Pinard, Pascal
中科院分区：
文献类型：
--
作者：
Kuzmic, Mira;Linares, Gerard Castro;Verdier-Pinard, Pascal
Septins是GTP结合蛋白的一个家族，其组装成更高级的结构，与膜、肌动蛋白丝和微管连接，因此是细胞结构的重要调节剂。Septin 9（SEPT 9）在肿瘤中经常过表达，并在遗传性神经痛性肌萎缩症（HNA）中突变，介导Septin与微管的结合，但这种相互作用的分子决定因素仍然不确定。我们证明了SEPT 9亚型1（SEPT9_i1）特有的短微管相关蛋白（MAP）样基序驱动细胞和体外重建中的septin八聚体-微管相互作用。隔蛋白-微管缔合需要携带SEPT9_i1的可聚合隔蛋白八聚体。虽然在MAP样基序之外，HNA突变废除了这种关联，确定了一个推定的调节结构域。从SEPT9_i1中去除该结构域可隔离微管上的隔膜蛋白，促进微管稳定性并改变肌动球蛋白纤维的分布和张力。因此，我们确定了关键的分子决定因素和潜在的调控作用的septin-microtubule相互作用，铺平了道路，破译的机制septin-associated pathology.This文章有一个相关的第一人称采访的论文的第一作者。
Septins, a family of GTP-binding proteins that assemble into higher order structures, interface with the membrane, actin filaments and microtubules, and are thus important regulators of cytoarchitecture. Septin 9 (SEPT9), which is frequently overexpressed in tumors and mutated in hereditary neuralgic amyotrophy (HNA), mediates the binding of septins to microtubules, but the molecular determinants of this interaction remained uncertain. We demonstrate that a short microtubule-associated protein (MAP)-like motif unique to SEPT9 isoform 1 (SEPT9_i1) drives septin octamer-microtubule interaction in cells and in vitro reconstitutions. Septin-microtubule association requires polymerizable septin octamers harboring SEPT9_i1. Although outside of the MAP-like motif, HNA mutations abrogate this association, identifying a putative regulatory domain. Removal of this domain from SEPT9_i1 sequesters septins on microtubules, promotes microtubule stability and alters actomyosin fiber distribution and tension. Thus, we identify key molecular determinants and potential regulatory roles of septin-microtubule interaction, paving the way to deciphering the mechanisms underlying septin-associated pathologies.This article has an associated First Person interview with the first author of the paper.