Abstract
Membrane fusion mediates a number of fundamental biological processes such as intracellular membrane trafficking, fertilization, and viral infection. Biological membranes are composed of lipids and proteins; while lipids generally play a structural role, proteins mediate specific functions in the membrane. Likewise, although proteins are key players in the fusion of biological membranes, there is emerging evidence supporting a functional role of lipids in various membrane fusion events. Intracellular membrane fusion is mediated by two protein families: SNAREs and membrane-bound GTPases. SNARE proteins are involved in membrane fusion between transport vesicles and their target compartments, as well as in homotypic fusion between organelles of the same type. Membrane-bound GTPases mediate mitochondrial fusion and homotypic endoplasmic reticulum fusion. Certain membrane lipids, known as regulatory lipids, regulate these membrane fusion events by directly affecting the function of membrane-bound GTPases, instead of simply changing the biophysical and biochemical properties of lipid bilayers. In this review, we provide a summary of the current understanding of how regulatory lipids affect GTPase-mediated intracellular membrane fusion by focusing on the functions of regulatory lipids that directly affect fusogenic GTPases.
Highlights
Membrane fusion is a vital step of a variety of fundamental processes in the cell and can be defined as a merger of two membrane-enclosed compartments into a single compartment
Consistent with this idea, mutant Sey1p lacking the sterol-binding motifs is unable to interact with Sec22p (Lee et al, 2019), an endoplasmic reticulum (ER) SNARE involved in Sey1pdependent ER fusion (Lee et al, 2015), supporting the notion that the binding of cholesterol to Sey1p affects the overall conformation of the protein, resulting in modification of its fusogenic activity as well as of the profiles of its interacting proteins (Figure 3A)
This review describes the role of regulatory lipids in GTPasemediated intracellular membrane fusion, focusing on examples of how these lipids affect proteins involved in membrane fusion processes
Summary
Proteins are key players in the fusion of biological membranes, there is emerging evidence supporting a functional role of lipids in various membrane fusion events. Intracellular membrane fusion is mediated by two protein families: SNAREs and membrane-bound GTPases. SNARE proteins are involved in membrane fusion between transport vesicles and their target compartments, as well as in homotypic fusion between organelles of the same type. Membrane-bound GTPases mediate mitochondrial fusion and homotypic endoplasmic reticulum fusion. Known as regulatory lipids, regulate these membrane fusion events by directly affecting the function of membranebound GTPases, instead of changing the biophysical and biochemical properties of lipid bilayers.
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