Lee S, Han J W, Leeper L, Gruver J S, Chung C Y
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232-6600, USA.
Biochim Biophys Acta. 2009 Jul;1793(7):1199-209. doi: 10.1016/j.bbamcr.2009.04.012. Epub 2009 May 3.
Previous study demonstrated that WASP localizes on vesicles during Dictyostelium chemotaxis and these vesicles appear to be preferentially distributed at the leading and trailing edge of migrating cells. In this study, we have examined the role of PCH family proteins, Nwk/Bzz1p-like protein (NLP) and Syndapin-like protein (SLP), in the regulation of the formation and trafficking of WASP-vesicles during chemotaxis. NLP and SLP appear to be functionally redundant and deletion of both nlp and slp genes causes the loss of polarized F-actin organization and significant defects in chemotaxis. WASP and NLP are colocalized on vesicles and interactions between two molecules via the SH3 domain of NLP/SLP and the proline-rich repeats of WASP are required for vesicle formation from Golgi. Microtubules are required for polarized trafficking of these vesicles as vesicles showing high directed mobility are absent in cells treated with nocodazole. Our results suggest that interaction of WASP with NLP/SLP is required for the formation and trafficking of vesicles from Golgi to the membrane, which might play a central role in the establishment of cell polarity during chemotaxis.
先前的研究表明,在盘基网柄菌趋化作用过程中,WASP定位于囊泡上,并且这些囊泡似乎优先分布在迁移细胞的前缘和后缘。在本研究中,我们研究了PCH家族蛋白、Nwk/Bzz1p样蛋白(NLP)和Syndapin样蛋白(SLP)在趋化作用过程中对WASP囊泡形成和运输的调节作用。NLP和SLP似乎在功能上是冗余的,nlp和slp基因的缺失会导致极化的F-肌动蛋白组织丧失以及趋化作用出现显著缺陷。WASP和NLP共定位于囊泡上,通过NLP/SLP的SH3结构域与WASP富含脯氨酸的重复序列之间的两个分子相互作用是从高尔基体形成囊泡所必需的。微管是这些囊泡极化运输所必需的,因为在用诺考达唑处理的细胞中不存在显示高定向迁移率的囊泡。我们的结果表明,WASP与NLP/SLP的相互作用是从高尔基体到膜的囊泡形成和运输所必需的,这可能在趋化作用过程中细胞极性的建立中起核心作用。