Role of kinesin light chain 1 in binding to specific cargoes.

Award Number
Status / Stage
1 July 2021 -
30 June 2024
Duration (calculated)
02 years 11 months
Funding Amount
Funder/Grant study page
Contracted Centre
The University of Manchester
Principal Investigator
Professor Viki Allan
PI Contact
WHO Catergories
Understanding Underlying Disease
Disease Type
Dementia (Unspecified)

CPEC Review Info
Reference ID732
ResearcherReside Team


Award NumberBB/V008307/1
Status / StageActive
Start Date20210701
End Date20240630
Duration (calculated) 02 years 11 months
Funder/Grant study pageBBSRC UKRI
Contracted CentreThe University of Manchester
Funding Amount£569,102.00


Kinesin-1-driven transport is essential for cell function in most eukaryotes, due in part to the wide variety of cargoes it carries, ranging from membrane organelles through to cytoskeletal proteins. Kinesin-1 consists of two motor subunits and two light chains (KLCs). Multiple genes encode each subunit, with further complexity provided by alternative splicing of the KLC1 gene, giving isoforms that differ widely in their C-terminal domain and have been implicated in human disease. An attractive hypothesis is that this variation enables kinesin-1 to bind to and transport such a plethora of cargo. Our overall aim is to uncover the specific roles palyed by KLC1 isoforms in membrane traffic, focusing on the early endocytic pathway. Using a mass spectrometry-based proximity biotinylation approach (BioID), we identified three endosome-associated proteins as near-neighbours of KLC1D, but not KLC2 or 3. Two of these play key roles in sorting and recycling material from the endosome via the ESCPE-1 and Retriever pathways while the third is involved in the recruitment of recycling endosomes to the midbody as an essential step in cytokinesis. We will determine how kinesin containing KLC1D contributes to these vital processes. To do this, we will establish a novel tool-box for manipulating the function of KLC1, including a new dominant-negative construct approach, and the development of a cell line with a degron tag inserted into the KLC1 gene. Upon auxin addition, the KLC1 protein will be rapidly degraded, giving an acute means of depleting kinesin containing KLC1. These tools will be very useful right across the kinesin field. We will also test if other KLC1 isoforms have shared or distinct roles compared to KLC1D by extending our BioID approach to identify specific membrane cargoes and interactors of three additional key KLC1 splice forms. Altogether, this project will provide the first molecular insight into how KLC1 splicing affects kinesin function.


Our overall aim is to uncover the specific roles palyed by KLC1 isoforms in membrane traffic, focusing on the early endocytic pathway.