Hegsted Anna, Wright Forrest A, Votra SarahBeth, Pruyne David
Department of Cell and Developmental Biology, State University of New York Upstate Medical University, Syracuse, New York, 13210.
Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, New York, 13210.
Cytoskeleton (Hoboken). 2016 Dec;73(12):712-728. doi: 10.1002/cm.21341. Epub 2016 Nov 9.
Formins are regulators of actin filament dynamics. We demonstrate here that two formins, FHOD-1 and EXC-6, are important in the nematode Caenorhabditis elegans for ovulation, during which actomyosin contractions push a maturing oocyte from the gonad arm into a distensible bag-like organ, the spermatheca. EXC-6, a homolog of the disease-associated mammalian formin INF2, is highly expressed in the spermatheca, where it localizes to cell-cell junctions and to circumferential actin filament bundles. Loss of EXC-6 does not noticeably affect the organization the actin filament bundles, and causes only a very modest increase in the population of junction-associated actin filaments. Despite absence of a strong cytoskeletal phenotype, approximately half of ovulations in exc-6 mutants exhibit extreme defects, including failure of the oocyte to enter the spermatheca, or breakage of the oocyte as the distal spermatheca entrance constricts during ovulation. Loss of FHOD-1 alone has little effect, and we cannot detect FHOD-1 in the spermatheca. However, combined loss of these formins in double fhod-1;exc-6 mutants results in profound ovulation defects, with significant slowing of the entry of oocytes into the spermatheca, and failure of nearly 80% of ovulations. We suggest that EXC-6 plays a role directly in the spermatheca, perhaps by modulating the ability of the spermatheca wall to rapidly accommodate an incoming oocyte, while FHOD-1 may play an indirect role relating to its known importance in the growth and function of the egg-laying muscles. © 2016 The Authors. Cytoskeleton Published by Wiley Periodicals, Inc.
formin蛋白是肌动蛋白丝动力学的调节因子。我们在此证明,两种formin蛋白,FHOD-1和EXC-6,在线虫秀丽隐杆线虫的排卵过程中起着重要作用,在此过程中,肌动球蛋白收缩将成熟的卵母细胞从性腺臂推入一个可扩张的袋状器官——受精囊。EXC-6是与疾病相关的哺乳动物formin蛋白INF2的同源物,在受精囊中高度表达,它定位于细胞间连接和周向肌动蛋白丝束。EXC-6的缺失对肌动蛋白丝束的组织没有明显影响,仅使与连接相关的肌动蛋白丝数量略有增加。尽管没有强烈的细胞骨架表型,但exc-6突变体中约一半的排卵表现出极端缺陷,包括卵母细胞无法进入受精囊,或在排卵过程中随着受精囊远端入口收缩而导致卵母细胞破裂。单独缺失FHOD-1影响不大,且我们在受精囊中检测不到FHOD-1。然而,在fhod-1;exc-6双突变体中这些formin蛋白的联合缺失会导致严重的排卵缺陷,卵母细胞进入受精囊的速度显著减慢,近80%的排卵失败。我们认为,EXC-6可能直接在受精囊中发挥作用,也许是通过调节受精囊壁快速容纳进入的卵母细胞的能力,而FHOD-1可能发挥间接作用,与其在产卵肌肉生长和功能中的已知重要性有关。© 2016作者。细胞骨架由威利期刊公司出版。