PT  - JOURNAL ARTICLE
AU  - Zuriñe Antón
AU  - Johannes F. Weijman
AU  - Christopher Williams
AU  - Edmund R.R. Moody
AU  - Judith Mantell
AU  - Yan Y. Yip
AU  - Jessica A. Cross
AU  - Tom A. Williams
AU  - Roberto A. Steiner
AU  - Matthew Crump
AU  - Derek N. Woolfson
AU  - Mark P. Dodding
TI  - Molecular mechanism for kinesin-1 direct membrane recognition
AID  - 10.1101/2021.01.20.427326
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.01.20.427326
4099  - http://biorxiv.org/content/early/2021/01/21/2021.01.20.427326.short
4100  - http://biorxiv.org/content/early/2021/01/21/2021.01.20.427326.full
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 carboxy-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 newly defined subset of long kinesin light chain paralogues and splice isoforms. This helix mediates the direct binding of kinesin-1 to lipid membranes. Membrane binding requires specific anionic phospholipids and is important for 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 new protein-lipid coincidence detection framework for kinesin-1 mediated organelle transport.Competing Interest StatementThe authors have declared no competing interest.