journal article·2021-02-25Open access

FAM134B-RHD Protein Clustering Drives Spontaneous Budding of Asymmetric Membranes

Marc Siggel, Ramachandra M. Bhaskara, Melanie K. Moesser, Ivan D̵ikić, Gerhard Hummer

Abstract

Living cells constantly remodel the shape of their lipid membranes. In the endoplasmic reticulum (ER), the reticulon homology domain (RHD) of the reticulophagy regulator 1 (RETR1/FAM134B) forms dense autophagic puncta that are associated with membrane removal by ER-phagy. In molecular dynamics (MD) simulations, we find that FAM134B-RHD spontaneously forms clusters, driven in part by curvature-mediated attractions. At a critical size, as in a nucleation process, the FAM134B-RHD clusters induce the formation of membrane buds. The kinetics of budding depends sensitively on protein concentration and bilayer asymmetry. Our MD simulations shed light on the role of FAM134B-RHD in ER-phagy and show that membrane asymmetry can be used to modulate the kinetic barrier for membrane remodeling.
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Research context

OpenAlex topics: Lipid Membrane Structure and Behavior · Cellular transport and secretion · Endoplasmic Reticulum Stress and Disease

SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.

Affiliations

Department of Theoretical Biophysics, Max Planck Institute of Biophysics, Max-von-Laue Str. 3, 60438 Frankfurt am Main, Germany

Institute of Biochemistry II, Faculty of Medicine, Goethe University Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany

Buchmann Institute of Molecular Life Sciences, Goethe University Frankfurt, Max-von-Laue Straße 15, 60438 Frankfurt am Main, Germany

Max Planck Institute of Biophysics, 60438 Frankfurt am Main, Germany

Institute of Biophysics, Goethe University Frankfurt, 60438 Frankfurt am Main, Germany

Funding

Deutsche Forschungsgemeinschaft · Max-Planck-Gesellschaft · Hessisches Ministerium f?r Wissenschaft und Kunst

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