Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
ReviewSMP-domain proteins at membrane contact sites: Structure and function☆
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).
References (34)
- et al.
Membrane contact sites, gateways for lipid homeostasis
Curr. Opin. Cell Biol.
(Apr 2015) - et al.
Inter-organelle membrane contact sites: through a glass, darkly
Curr. Opin. Cell Biol.
(Aug 2006) - et al.
ER–PM connections: sites of information transfer and inter-organelle communication
Curr. Opin. Cell Biol.
(Aug 2013) PI(4,5)P(2)-dependent and Ca(2 +)-regulated ER–PM interactions mediated by the extended synaptotagmins
Cell
(Jun 20 2013)Structure and Ca(2)(+)-binding properties of the tandem C(2) domains of E-Syt2
Structure
(Feb 4 2014)- et al.
Mechanisms of membrane fusion: disparate players and common principles
Nat. Rev. Mol. Cell Biol.
(Jul 2008) - et al.
ER–mitochondria contact sites in yeast: beyond the myths of ERMES
Curr. Opin. Cell Biol.
(Aug 2015) Composition and topology of the endoplasmic reticulum–mitochondria encounter structure
J. Mol. Biol.
(Nov 4 2011)Lam6 regulates the extent of contacts between organelles
Cell Rep.
(Jul 7 2015)- et al.
StARTing to understand membrane contact sites
Trends Cell Biol.
(Sep 2015)
A conserved membrane-binding domain targets proteins to organelle contact sites
J. Cell Sci.
Homology of SMP domains to the TULIP superfamily of lipid-binding proteins provides a structural basis for lipid exchange between ER and mitochondria
Bioinformatics
Diverse membrane-associated proteins contain a novel SMP domain
FASEB J.
Structure of a lipid-bound extended synaptotagmin indicates a role in lipid transfer
Nature
ER-to-plasma membrane tethering proteins regulate cell signaling and ER morphology
Dev. Cell
An ER–mitochondria tethering complex revealed by a synthetic biology screen
Science
The ancient and widespread nature of the ER–mitochondria encounter structure
Mol. Biol. Evol.
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.