Molecular mechanism for kinesin-1 direct membrane recognition

Zuriñe Antón; Johannes F. Weijman; Christopher Williams; Edmund R.R. Moody; Judith Mantell; Yan Y. Yip; Jessica A. Cross; Tom A. Williams; Roberto A. Steiner; Matthew P. Crump; Derek N. Woolfson; Mark P. Dodding

doi:10.1126/sciadv.abg6636

Molecular mechanism for kinesin-1 direct membrane recognition

Zuriñe Antón, Johannes F. Weijman, Christopher Williams, Edmund R.R. Moody, Judith Mantell, Yan Y. Yip, Jessica A. Cross, Tom A. Williams, Roberto A. Steiner, Matthew P. Crump, Derek N. Woolfson, Mark P. Dodding^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

6 Citations (Scopus)

Abstract

The cargo-binding capabilities of cytoskeletal motor proteins have expanded during evolution through both gene duplication and alternative splicing. For the light chains of the kinesin-1 family of microtubule motors, this has resulted in an array of carboxyl-terminal domain sequences of unknown molecular function. Here, combining phylogenetic analyses with biophysical, biochemical, and cell biology approaches, we identify a highly conserved membrane-induced curvature-sensitive amphipathic helix within this region of a subset of long kinesin light-chain paralogs and splice isoforms. This helix mediates the direct binding of kinesin-1 to lipid membranes. Membrane binding requires specific anionic phospholipids, and it contributes to kinesin-1–dependent lysosome positioning, a canonical activity that, until now, has been attributed exclusively the recognition of organelle-associated cargo adaptor proteins. This leads us to propose a protein-lipid coincidence detection framework for kinesin-1–mediated organelle transport.

Original language	English
Article number	eabg6636
Journal	Science Advances
Volume	7
Issue number	31
DOIs	https://doi.org/10.1126/sciadv.abg6636
Publication status	Published - Jul 2021

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title = "Molecular mechanism for kinesin-1 direct membrane recognition",

abstract = "The cargo-binding capabilities of cytoskeletal motor proteins have expanded during evolution through both gene duplication and alternative splicing. For the light chains of the kinesin-1 family of microtubule motors, this has resulted in an array of carboxyl-terminal domain sequences of unknown molecular function. Here, combining phylogenetic analyses with biophysical, biochemical, and cell biology approaches, we identify a highly conserved membrane-induced curvature-sensitive amphipathic helix within this region of a subset of long kinesin light-chain paralogs and splice isoforms. This helix mediates the direct binding of kinesin-1 to lipid membranes. Membrane binding requires specific anionic phospholipids, and it contributes to kinesin-1–dependent lysosome positioning, a canonical activity that, until now, has been attributed exclusively the recognition of organelle-associated cargo adaptor proteins. This leads us to propose a protein-lipid coincidence detection framework for kinesin-1–mediated organelle transport.",

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note = "Publisher Copyright: Copyright {\textcopyright} 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.",

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doi = "10.1126/sciadv.abg6636",

language = "English",

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AU - Antón, Zuriñe

AU - Weijman, Johannes F.

AU - Williams, Christopher

AU - Moody, Edmund R.R.

AU - Mantell, Judith

AU - Yip, Yan Y.

AU - Cross, Jessica A.

AU - Williams, Tom A.

AU - Steiner, Roberto A.

AU - Crump, Matthew P.

AU - Woolfson, Derek N.

AU - Dodding, Mark P.

N1 - Publisher Copyright: Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

PY - 2021/7

Y1 - 2021/7

N2 - The cargo-binding capabilities of cytoskeletal motor proteins have expanded during evolution through both gene duplication and alternative splicing. For the light chains of the kinesin-1 family of microtubule motors, this has resulted in an array of carboxyl-terminal domain sequences of unknown molecular function. Here, combining phylogenetic analyses with biophysical, biochemical, and cell biology approaches, we identify a highly conserved membrane-induced curvature-sensitive amphipathic helix within this region of a subset of long kinesin light-chain paralogs and splice isoforms. This helix mediates the direct binding of kinesin-1 to lipid membranes. Membrane binding requires specific anionic phospholipids, and it contributes to kinesin-1–dependent lysosome positioning, a canonical activity that, until now, has been attributed exclusively the recognition of organelle-associated cargo adaptor proteins. This leads us to propose a protein-lipid coincidence detection framework for kinesin-1–mediated organelle transport.

AB - The cargo-binding capabilities of cytoskeletal motor proteins have expanded during evolution through both gene duplication and alternative splicing. For the light chains of the kinesin-1 family of microtubule motors, this has resulted in an array of carboxyl-terminal domain sequences of unknown molecular function. Here, combining phylogenetic analyses with biophysical, biochemical, and cell biology approaches, we identify a highly conserved membrane-induced curvature-sensitive amphipathic helix within this region of a subset of long kinesin light-chain paralogs and splice isoforms. This helix mediates the direct binding of kinesin-1 to lipid membranes. Membrane binding requires specific anionic phospholipids, and it contributes to kinesin-1–dependent lysosome positioning, a canonical activity that, until now, has been attributed exclusively the recognition of organelle-associated cargo adaptor proteins. This leads us to propose a protein-lipid coincidence detection framework for kinesin-1–mediated organelle transport.

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Molecular mechanism for kinesin-1 direct membrane recognition

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