MLN64

Metastatic lymph node 64 protein (MLN64 or STARD3) is a late endosomal integral membrane protein involved in cholesterol transport.^[1]

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Function

MLN64 is hypothesized to regulate cholesterol transport between the late endosome and cytoplasmic membranes. It has also been proposed to mediate StAR-independent steroidogenesis, such as in the human placenta.^[2]

Structure

Its C-terminus contains a StAR-related transfer domain (START) that is homologous to the steroidogenic acute regulatory protein (StAR). X-ray crystallography indicates that this domain forms a pocket that can bind cholesterol.^[3] Its N-terminus consists of a MENTAL (MLN64 N-terminal) domain similar to the protein MLN64 N-terminal homologue (MENTHO) with unclear function.

Production

MLN64 is expressed in all tissues in the body at various levels. In the brain, MLN64 is detectable in many but not all cells.^[4] Many malignant tumors highly express MLN64 as a result of its gene being part of a Her2/erbB2-containing gene locus that is duplicated.

Pathology

Loss of MLN64 has little effect in mice.^[5] At the cellular level, changes in MLN64 can disrupt trafficking of endosomes and cause accumulation of cholesterol in late endosomes.

References

1. ^ Alpy F, Tomasetto C. MLN64 and MENTHO, two mediators of endosomal cholesterol transport. Biochem Soc Trans. 2006 Jun;34(Pt 3):343-5. PMID: 16709157
2. ^ Watari H, Arakane F, Moog-Lutz C, Kallen CB, Tomasetto C, Gerton GL, Rio MC, Baker ME, Strauss III JF. MLN64 contains a domain with homology to the steroidogenic acute regulatory protein (StAR) that stimulates steroidogenesis. Proc Natl Acad Sci USA 94(16):8462-7, 1997. PMID: 9237999
3. ^ Tsujishita, Y., and Hurley, J.H. (2000). Structure and lipid transport mechanism of a StAR-related domain. Nature Struct. Biol. 7, 408-414.
4. ^ King SR, Smith AG, Alpy F, Tomasetto C, Ginsberg SD, Lamb DJ. Characterization of the putative cholesterol transport protein metastatic lymph node 64 in the brain. Neuroscience 139(3):1031-8, 2006. PMID: 16549269
5. ^ Kishida T, Kostetskii I, Zhang Z, Martinez F, Liu P, Walkley SU, Dwyer NK, Blanchette-Mackie EJ, Radice GL, Strauss III JF. Targeted mutation of the MLN64 START domain causes only modest alterations in cellular sterol metabolism. J Biol Chem 2004;279(18):19276-85. PMID: 14963026

External links

• MeSH MLN64+protein,+human