Intersectin 2 controls actin cap formation and meiotic division in mouse oocytes through the Cdc42 pathway. Issue 10 (19th September 2017)

• Record Type: Journal Article
• Authors: Zhang, Jiaqi; Ma, Rujun; Li, Ling; Wang, Lina; Hou, Xiaojing; Han, Longsen; Ge, Juan; Li, Mo; Wang, Qiang
• Is Part Of: FASEB journal. Volume 31:Issue 10(2017)
• Page Start: 4277
• Page End: 4285
• Publication Date: 2017-09-19
• Subjects: meiosis -- spindle -- chromosome -- polarization -- cytokinesis; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201700179R
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: Intersectins (ITSNs), an evolutionarily conserved adaptor protein family, have been implicated in multiple biologic processes; however, their functions in mammalian oocytes have not been addressed. Here, we report delayed meiotic resumption and defective cytokinesis upon specific depletion of ITSN2 in mouse oocytes. In particular, abnormal spindle, misaligned chromosomes, and loss of cortical actin cap are readily observed in LTSN2‐depleted oocytes. Similarly, a small molecule that targets the Cdc42–ITSN interaction also disrupts oocyte maturation and actin polymerization. Moreover, we find that ITSN2 depletion reduces the activity of Cdc42 in oocytes and, of note, that forced expression of the dominant‐positive mutant of Cdc42, in part, prevents the effects of ITSN2 knockdown on actin cap formation. In addition, the localization of WASP and Arp2, the downstream effector proteins of Cdc42, is altered in ITSN2‐depleted oocytes accordingly. In summary, our data support a model in which ITSN2 depletion induces the inactivation of Cdc42, which, in turn, influences the distribution and function of Arp2/3 and WASP, consequently disrupting oocyte polarity establishment and meiotic division.—Zhang, J., Ma, R., Li, L., Wang, L., Hou, X., Han, L., Ge, J., Li, M., Wang, Q. Intersectin 2 controls actin cap formation and meiotic division in mouse oocytes through the Cdc42 pathway. FASEB J. 31, 4277–4285 (2017). www.fasebj.org