Mahogunin-mediated regulation of Gai localisation during mitosis and its effect on spindle positioning

• Published in: Biochemistry and cell biology Vol. 94; no. 4; p. 359
• Main Authors: Srivastava, Devika, Mukherjee, Rukmini, Mookherjee, Debdatto, Chakrabarti, Oishee
• Format: Journal Article
• Language: English
• Published: Ottawa Canadian Science Publishing NRC Research Press 01.08.2016
• Subjects: Cell culture; Cell division; Gene expression; Mutation; Proteins
• ISSN: 0829-8211; 1208-6002

Mahogunin RING Finger 1 (MGRN1) is a ubiquitin E3 ligase known to affect spindle tilt in mitotic cells by regulating α-tubulin ubiquitination and polymerization. In cell culture systems we have found that expressing truncated mutants of MGRN1 leads to various other mitotic anomalies, such as lateral and angular spindle displacements. This seems to be independent of the MGRN1 ligase activity. Our experiments suggest that MGRN1 regulates the balance between the lower molecular weight monomeric Gα^sub i^ and larger trimeric G-protein complex, along with its abundance in the ternary complex that regulates spindle positioning. The cytosolic isoforms of MGRN1 lead to the enrichment of monomeric Gα^sub i^ in the cytosol and its subsequent recruitment at the plasma membrane. Excess Gα^sub i^ at the cell cortex results in an imbalance in the assembly of the ternary complex regulating spindle positioning during mitosis. These observations seem independent of the ligase activity of MGRN1, although we cannot exclude the involvement of an intermediate player that acts as a substrate for MGRN1, and in turn, regulates Gα^sub i^.