The novel MIT-domain-containing protein MITD1 interacts with ESCRT-III proteins and functions in cytokinesis

Tuesday, October 25, 2011 — Poster Session II
Noon – 2:00 p.m.	Natcher Conference Center	NINDS	CELLBIO-11

* FARE Award Winner

Authors

• S Lee
• A Tipirneni
• C Blackstone

Abstract

The endosomal sorting complex required for transport (ESCRT) proteins are required for the membrane-abscission step of cytokinesis. Midbody recruitment of the ESCRT-III proteins are regulated by interactions with microtubule interacting and transport (MIT)-domain-containing proteins including VPS4 and spastin. Even though many proteins have been rapidly identified as MIT-domain-containing proteins, their functional relationship with the ESCRT-III complex is not fully understood. Here we identify MIT-domain containing protein 1 (MITD1) as an interacting partner of ESCRT-III proteins. MITD1 localizes to the midbody during cytokinesis. When interactions of MITD1 with all ESCRT-III proteins are examined by yeast-two hybrid assay, only CHMP1A/B, CHMP2A and IST1 show specific interactions with MITD1. Interestingly, sequence analysis revealed MIT-domain of MITD1 is very similar to that of VPS4. The VPS4 residues identified by structural studies as required for interaction with ESCRT-III are highly conserved in MITD1. Mutations in these residues of MITD1 inhibit both the interactions with ESCRT-III and its midbody localization. Depletion of MITD1 increases the number of multinucleated cells, reflecting impaired cytokinesis. Midbody recruitment of CHMP1B and IST1 is also inhibited by MITD1 depletion. Our findings will provide a better understanding of the functional interactions of MIT-domain-containing proteins with ESCRT complexes.

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