Review
SMP-domain proteins at membrane contact sites: Structure and function

https://doi.org/10.1016/j.bbalip.2015.12.003Get rights and content

Highlights

  • SMP-domain proteins tether apposing membranes at contact sites.

  • SMP-domain proteins bind glycerolipid.

  • SMP-domain proteins likely mediate glycerolipid transfer at contact sites.

Abstract

SMP-domains are found in proteins that localize to membrane contact sites. Elucidation of the properties of these proteins gives clues as to the molecular bases underlying processes that occur at such sites. Described here are recent discoveries concerning the structure, function, and regulation of the Extended-Synaptotagmin proteins and ERMES complex subunits, SMP-domain proteins at endoplasmic reticulum (ER)–plasma membrane and ER–mitochondrial contacts, respectively. They act as tethers contributing to the architecture of these sites and as lipid transporters that convey glycerolipids between apposed membranes. This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.

Section snippets

Extended-Synaptotagmins

The E-Syts act as tethers between the ER and plasma membrane [8], [9]. Each E-Syt has an N-terminal β-hairpin embedded in the ER membrane [9], which is followed by the SMP domain and three to five C2 modules in the C-terminal portion of the molecule (Fig. 1A). Nomenclature for these proteins derives from their distant resemblance to synaptotagmin, the Ca2 + sensor for exocytosis, which has an N-terminal membrane anchor followed by two C2 domains [12]. C2 domains, including those of

ERMES complex

ER–mitochondria contact sites are very abundant. Among their multiple functions they provide conduits for Ca2 + exchange between the two organelles and for the transfer of specific lipids. As the mitochondria are not part of the secretory pathway, it has long been appreciated that they import many of their membrane lipids independently of vesicle trafficking. Additionally, the partnership between ER and mitochondria plays a role in the metabolism of specific lipids, most notably PE [27]. The

Future directions

Future developments will hopefully address how the E-Syts, ERMES, and other SMP-domain proteins extract, recognize and deliver lipids, whether they transport lipids vectorially and, if so, which mechanisms underlie vectorial transport, and how their activities at contact sites can be regulated. As yeast studies have shown that neither the E-Syts nor the ERMES complex is essential for cellular life [8], [10], their interplay or redundancy with other lipid transport proteins will also have to be

Acknowledgments

We thank Dr. Pascal Egea for providing model coordinates for the Mmm1–Mdm12 subcomplex of ERMES (panel F in Fig. 1), and we are grateful to the members of our labs for their comments regarding this manuscript. Work in the authors' labs is supported by grants from the NIH (GM080616 and GM114068 to KMR and R37NS036251 and DK082700 to PDC).

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  • Cited by (0)

    This article is part of a Special Issue entitled: The cellular lipid landscape edited by Tim P. Levine and Anant K. Menon.

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