Article open access publication

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

Cell Reports, Elsevier, ISSN 2211-1247

Volume 23, 7, 2018

DOI:10.1016/j.celrep.2018.04.074, Dimensions: pub.1103995948, PMID: 29768204,

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  1. (1) University of Copenhagen, grid.5254.6, KU
  2. (2) Cornell University, grid.5386.8

Description

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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University of Copenhagen

Danish Open Access Indicator

2018: Realized

Research area: Medicine

Danish Bibliometrics Indicator

2018: Level 2

Research area: Medicine

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Times Cited: 12

Field Citation Ratio (FCR): 3.88

Relative Citation ratio (RCR): 1.5

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