The ARF GAPs ELMOD1 and ELMOD3 act at the Golgi and cilia to regulate ciliogenesis and ciliary protein traffic.
The ARF GAPs ELMOD1 and ELMOD3 act at the Golgi and cilia to regulate ciliogenesis and ciliary protein traffic.
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DOI：
10.1091/mbc.e21-09-0443
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发表时间：
2022-02-01
影响因子：
3.3
通讯作者：
Kahn, Richard A.
中科院分区：
文献类型：
--
作者：
Turn, Rachel E.;Hu, Yihan;Dewees, Skylar, I;Devi, Narra;East, Michael P.;Hardin, Katherine R.;Khatib, Tala;Linnert, Joshua;Wolfrum, Uwe;Lim, Michael J.;Casanova, James E.;Caspary, Tamara;Kahn, Richard A.
ELMOD 是由三种哺乳动物旁系同源物组成的家族，对一系列独特的 ADP 核糖基化因子 (ARF) 家族 GTP 酶（包括 ARF 样 (ARL) 蛋白）表现出 GTP 酶激活蛋白 (GAP) 活性。 ELMOD在哺乳动物组织中普遍表达，在真核生物中高度保守，并且起源古老，存在于最后的真核共同祖先中。我们描述了 ELMOD2 在永生化小鼠胚胎成纤维细胞 (MEF) 中调节细胞分裂、微管、纤毛发生和线粒体融合的功能。在这里，我们使用与旁系同源物 ELMOD1 和 ELMOD3 类似的策略，确定了这些细胞调节因子的新功能和位置，并将它们与 ELMOD2 的功能和位置进行比较，从而确定家族成员之间的功能冗余。我们发现 Elmod1 或 Elmod3 缺失所产生的表型有很强的相似性，而与 Elmod2 缺失系中产生的表型存在显着差异。 Elmod1 或 Elmod3 的缺失会导致细胞形成初级纤毛的能力下降、纤毛蛋白质子集的丢失以及一些纤毛蛋白质在高尔基体的积累，预计这是由于从高尔基体到纤毛的交通受损造成的。这些表型在激活 ARL3 或 ARL16 的突变体表达后发生逆转，将它们的作用与 ELMOD1/3 的作用联系起来。
ELMODs are a family of three mammalian paralogues that display GTPase-activating protein (GAP) activity toward a uniquely broad array of ADP-ribosylation factor (ARF) family GTPases that includes ARF-like (ARL) proteins. ELMODs are ubiquitously expressed in mammalian tissues, highly conserved across eukaryotes, and ancient in origin, being present in the last eukaryotic common ancestor. We described functions of ELMOD2 in immortalized mouse embryonic fibroblasts (MEFs) in the regulation of cell division, microtubules, ciliogenesis, and mitochondrial fusion. Here, using similar strategies with the paralogues ELMOD1 and ELMOD3, we identify novel functions and locations of these cell regulators and compare them to those of ELMOD2, allowing the determination of functional redundancy among the family members. We found strong similarities in phenotypes resulting from deletion of either Elmod1 or Elmod3 and marked differences from those arising in Elmod2 deletion lines. Deletion of either Elmod1 or Elmod3 results in the decreased ability of cells to form primary cilia, loss of a subset of proteins from cilia, and accumulation of some ciliary proteins at the Golgi, predicted to result from compromised traffic from the Golgi to cilia. These phenotypes are reversed upon activating mutant expression of either ARL3 or ARL16, linking their roles to ELMOD1/3 actions.