Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins

TY - JOUR

T1 - Membrane curvature induction and tubulation are common features of synucleins and apolipoproteins

AU - Varkey, Jobin

AU - Isas, Jose Mario

AU - Mizuno, Naoko

AU - Jensen, Martin Borch

AU - Bhatia, Vikram Kjøller

AU - Jao, Christine C

AU - Petrlova, Jitka

AU - Voss, John C

AU - Stamou, Dimitrios G

AU - Steven, Alasdair C

AU - Langen, Ralf

PY - 2010/10/15

Y1 - 2010/10/15

N2 - 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.

AB - 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.

KW - Animals

KW - Apolipoprotein A-I

KW - Cell Membrane

KW - Humans

KW - Liposomes

KW - Nerve Tissue Proteins

KW - alpha-Synuclein

KW - beta-Synuclein

U2 - 10.1074/jbc.M110.139576

DO - 10.1074/jbc.M110.139576

M3 - Journal article

C2 - 20693280

SN - 0021-9258

VL - 285

SP - 32486

EP - 32493

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

IS - 42

ER -