JOURNAL ARTICLE

An Amphipathic Helix Directs Cellular Membrane Curvature Sensing and Function of the BAR Domain Protein PICK1

Rasmus Herlo, Viktor K Lund, Matthew D Lycas, Anna M Jansen, George Khelashvili, Rita C Andersen, Vikram Bhatia, Thomas S Pedersen, Pedro B C Albornoz, Niklaus Johner, Ina Ammendrup-Johnsen, Nikolaj R Christensen, Simon Erlendsson, Mikkel Stoklund, Jannik B Larsen, Harel Weinstein, Ole Kjærulff, Dimitrios Stamou, Ulrik Gether, Kenneth L Madsen
Cell Reports 2018 May 15, 23 (7): 2056-2069
29768204
BAR domains are dimeric protein modules that sense, induce, and stabilize lipid membrane curvature. Here, we show that membrane curvature sensing (MCS) directs cellular localization and function of the BAR domain protein PICK1. In PICK1, and the homologous proteins ICA69 and arfaptin2, we identify an amphipathic helix N-terminal to the BAR domain that mediates MCS. Mutational disruption of the helix in PICK1 impaired MCS without affecting membrane binding per se. In insulin-producing INS-1E cells, super-resolution microscopy revealed that disruption of the helix selectively compromised PICK1 density on insulin granules of high curvature during their maturation. This was accompanied by reduced hormone storage in the INS-1E cells. In Drosophila, disruption of the helix compromised growth regulation. By demonstrating size-dependent binding on insulin granules, our finding highlights the function of MCS for BAR domain proteins in a biological context distinct from their function, e.g., at the plasma membrane during endocytosis.

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