Functional characterization of the MENTAL domain. - Archive ouverte HAL Access content directly
Journal Articles Journal of Biological Chemistry Year : 2005

Functional characterization of the MENTAL domain.

Abstract

Human metastatic lymph node (MLN) 64 is composed of two conserved regions. The amino terminus contains a conserved membrane-spanning MENTAL (MLN64 NH(2)-terminal) domain shared with an unique protein called MENTHO (MLN64 NH(2)-terminal domain homologue) and targets the protein to late endosome. The carboxyl-terminal domain is composed of a cholesterol binding steroidogenic acute regulatory-related lipid transfer domain exposed to the cytoplasm. MENTHO overexpression leads to the accumulation of enlarged endosomes. In this study, we show that MLN64 overexpression also induces the formation of enlarged endosomes, an effect that is probably mediated by the MENTAL domain. Using an in vivo photocholesterol binding assay, we find that the MENTAL domain of MLN64 is a cholesterol binding domain. Moreover, glutathione S-transferase pull-down or co-immunoprecipitation experiments demonstrate that this domain mediates homo- and hetero-interaction of MLN64 and MENTHO. In living cells, the expression of paired yellow fluorescent and cyan fluorescent fusion proteins show MENTHO homo-interaction and its interaction with MLN64. These data indicate that within late-endosomal membranes, MLN64 and MENTHO define discrete cholesterol-containing subdomains. The MENTAL domain might serve to maintain cholesterol at the membrane of late endosomes prior to its shuttle to cytoplasmic acceptor(s).

Dates and versions

hal-00187338 , version 1 (14-11-2007)

Identifiers

Cite

Fabien Alpy, Vinoth K Latchumanan, Valérie Kedinger, Agnes Janoshazi, Christoph Thiele, et al.. Functional characterization of the MENTAL domain.. Journal of Biological Chemistry, 2005, 280 (18), pp.17945-52. ⟨10.1074/jbc.M500723200⟩. ⟨hal-00187338⟩
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