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9.B.198 The Membrane-anchored Lipid-binding Protein (LAM) Family

Membrane contact sites are structures where two organelles come close together to regulate flow of material and information between them. One type of inter-organelle communication is lipid exchange, which must occur for membrane maintenance and in response to environmental and cellular stimuli. Soluble lipid transfer proteins have been extensively studied, but additional families of transfer proteins have been identified that are anchored into membranes by transmembrane helices. If such proteins target membrane contact sites, they may function in organellar lipid transfer. The eukaryotic family of so-called Lipid transfer proteins Anchored at Membrane contact sites (LAMs) all contain both a sterol-specific lipid transfer domain in the StARkin superfamily (related to StART/Bet_v1), and one or more transmembrane helices, anchoring them in the endoplasmic reticulum (ER). They target a variety of membrane contact sites, including contacts between organelles. Lam1-4p target punctate ER-plasma membrane contacts, while Lam5p and Lam6p target multiple contacts including vacuolar ER contacts. These developments confirm previous observations on tubular lipid-binding proteins (TULIPs) that establish the importance of membrane anchored proteins for lipid traffic (Wong and Levine 2016). However, it is not known if LAMs are transporters, or are regulators that affect traffic indirectly .

References associated with 9.B.198 family:

Elbaz-Alon, Y., M. Eisenberg-Bord, V. Shinder, S.B. Stiller, E. Shimoni, N. Wiedemann, T. Geiger, and M. Schuldiner. (2015). Lam6 Regulates the Extent of Contacts between Organelles. Cell Rep 12: 7-14. 26119743
Gatta, A.T., L.H. Wong, Y.Y. Sere, D.M. Calderón-Noreña, S. Cockcroft, A.K. Menon, and T.P. Levine. (2015). A new family of StART domain proteins at membrane contact sites has a role in ER-PM sterol transport. Elife 4:. 26001273
Laraia, L., A. Friese, D.P. Corkery, G. Konstantinidis, N. Erwin, W. Hofer, H. Karatas, L. Klewer, A. Brockmeyer, M. Metz, B. Schölermann, M. Dwivedi, L. Li, P. Rios-Munoz, M. Köhn, R. Winter, I.R. Vetter, S. Ziegler, P. Janning, Y.W. Wu, and H. Waldmann. (2019). The cholesterol transfer protein GRAMD1A regulates autophagosome biogenesis. Nat Chem Biol 15: 710-720. 31222192
Murley, A., R.D. Sarsam, A. Toulmay, J. Yamada, W.A. Prinz, and J. Nunnari. (2015). Ltc1 is an ER-localized sterol transporter and a component of ER-mitochondria and ER-vacuole contacts. J. Cell Biol. 209: 539-548. 25987606
Naito, T. and Y. Saheki. (2021). GRAMD1-mediated accessible cholesterol sensing and transport. Biochim. Biophys. Acta. Mol. Cell Biol. Lipids 1866: 158957. [Epub: Ahead of Print] 33932585
Wong, L.H. and T.P. Levine. (2016). Lipid transfer proteins do their thing anchored at membrane contact sites… but what is their thing? Biochem Soc Trans 44: 517-527. 27068964