title: Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins.
abstract: Synucleins and apolipoproteins have been implicated in a number of membrane and lipid trafficking events. Lipid interaction for both types of proteins is mediated by 11 amino acid repeats that form amphipathic helices. This similarity suggests that synucleins and apolipoproteins might have comparable effects on lipid membranes, but this has not been shown directly. Here, we find that α-synuclein, β-synuclein, and apolipoprotein A-1 have the conserved functional ability to induce membrane curvature and to convert large vesicles into highly curved membrane tubules and vesicles. The resulting structures are morphologically similar to those generated by amphiphysin, a curvature-inducing protein involved in endocytosis. Unlike amphiphysin, however, synucleins and apolipoproteins do not require any scaffolding domains and curvature induction is mediated by the membrane insertion and wedging of amphipathic helices alone. Moreover, we frequently observed that α-synuclein caused membrane structures that had the appearance of nascent budding vesicles. The ability to function as a minimal machinery for vesicle budding agrees well with recent findings that α-synuclein plays a role in vesicle trafficking and enhances endocytosis. Induction of membrane curvature must be under strict regulation in vivo; however, as we find it can also cause disruption of membrane integrity. Because the degree of membrane curvature induction depends on the concerted action of multiple proteins, controlling the local protein density of tubulating proteins may be important. How cellular safeguarding mechanisms prevent such potentially toxic events and whether they go awry in disease remains to be determined.
authors.affiliation: Zilkha Neurogenetic Institute, University of Southern California, Los Angeles, California 90033, USA.
authors.forename: Jobin
authors.initials: J
authors.lastname: Varkey
authors.forename: Jose Mario
authors.initials: JM
authors.lastname: Isas
authors.forename: Naoko
authors.initials: N
authors.lastname: Mizuno
authors.forename: Martin Borch
authors.initials: MB
authors.lastname: Jensen
authors.forename: Vikram Kjøller
authors.initials: VK
authors.lastname: Bhatia
authors.forename: Christine C
authors.initials: CC
authors.lastname: Jao
authors.forename: Jitka
authors.initials: J
authors.lastname: Petrlova
authors.forename: John C
authors.initials: JC
authors.lastname: Voss
authors.forename: Dimitrios G
authors.initials: DG
authors.lastname: Stamou
authors.forename: Alasdair C
authors.initials: AC
authors.lastname: Steven
authors.forename: Ralf
authors.initials: R
authors.lastname: Langen
mesh_terms: D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry* / Q000378:metabolism; D002462:Cell Membrane / Q000737:chemistry* / Q000648:ultrastructure; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism; D051846:beta-Synuclein / Q000737:chemistry* / Q000378:metabolism
chemical_list: D016632:Apolipoprotein A-I; D008081:Liposomes; D009419:Nerve Tissue Proteins; D051844:alpha-Synuclein; D051846:beta-Synuclein; C075637:amphiphysin