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GTP binding controls complex formation by the human ROCO protein MASL1

Dihanich, S., Civiero, L., Manzoni, C., Mamais, A., Bandopadhyay, R., Greggio, E. and Lewis, P. A. (2014) GTP binding controls complex formation by the human ROCO protein MASL1. FEBS Journal, 281 (1). pp. 261-274. ISSN 1742-464X

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To link to this item DOI: 10.1111/febs.12593

Abstract/Summary

The human ROCO proteins are a family of multi-domain proteins sharing a conserved ROC-COR supra-domain. The family has four members: leu- cine-rich repeat kinase 1 (LRRK1), leucine-rich repeat kinase 2 (LRRK2), death-associated protein kinase 1 (DAPK1) and malignant fibrous histiocy- toma amplified sequences with leucine-rich tandem repeats 1 (MASL1). Previous studies of LRRK1/2 and DAPK1 have shown that the ROC (Ras of complex proteins) domain can bind and hydrolyse GTP, but the cellular consequences of this activity are still unclear. Here, the first biochemical characterization of MASL1 and the impact of GTP binding on MASL1 complex formation are reported. The results demonstrate that MASL1, similar to other ROCO proteins, can bind guanosine nucleotides via its ROC domain. Furthermore, MASL1 exists in two distinct cellular com- plexes associated with heat shock protein 60, and the formation of a low molecular weight pool of MASL1 is modulated by GTP binding. Finally, loss of GTP enhances MASL1 toxicity in cells. Taken together, these data point to a central role for the ROC/GTPase domain of MASL1 in the reg- ulation of its cellular function.

Item Type:Article
Refereed:Yes
Divisions:Interdisciplinary centres and themes > Centre for Integrative Neuroscience and Neurodynamics (CINN)
Faculty of Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
ID Code:37256
Uncontrolled Keywords:complex formation;G-protein;HSP60;LRRK2;MASL1; ROCO
Publisher:Wiley

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