Cargando…

A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin

The activity of a kinesin is largely determined by the approximately 350 residue motor domain, and this region alone is sufficient to classify a kinesin as a member of a particular family. The kinesin-13 family are a group of microtubule depolymerizing kinesins and are vital regulators of microtubul...

Descripción completa

Detalles Bibliográficos
Autores principales: Belsham, Hannah R., Alghamdi, Hanan M., Dave, Nikita, Rathbone, Alexandra J., Wickstead, Bill, Friel, Claire T.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Royal Society 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428548/
https://www.ncbi.nlm.nih.gov/pubmed/36043268
http://dx.doi.org/10.1098/rsob.220133
_version_ 1784779143803568128
author Belsham, Hannah R.
Alghamdi, Hanan M.
Dave, Nikita
Rathbone, Alexandra J.
Wickstead, Bill
Friel, Claire T.
author_facet Belsham, Hannah R.
Alghamdi, Hanan M.
Dave, Nikita
Rathbone, Alexandra J.
Wickstead, Bill
Friel, Claire T.
author_sort Belsham, Hannah R.
collection PubMed
description The activity of a kinesin is largely determined by the approximately 350 residue motor domain, and this region alone is sufficient to classify a kinesin as a member of a particular family. The kinesin-13 family are a group of microtubule depolymerizing kinesins and are vital regulators of microtubule length. Kinesin-13s are critical to spindle assembly and chromosome segregation in both mitotic and meiotic cell division and play crucial roles in cilium length control and neuronal development. To better understand the evolution of microtubule depolymerization activity, we created a synthetic ancestral kinesin-13 motor domain. This phylogenetically inferred ancestral motor domain is the sequence predicted to have existed in the common ancestor of the kinesin-13 family. Here we show that the ancestral kinesin-13 motor depolymerizes stabilized microtubules faster than any previously tested depolymerase. This potent activity is more than an order of magnitude faster than the most highly studied kinesin-13, MCAK and allows the ancestral kinesin-13 to depolymerize doubly stabilized microtubules and cause internal breaks within microtubules. These data suggest that the ancestor of the kinesin-13 family was a ‘super depolymerizer’ and that members of the kinesin-13 family have evolved away from this extreme depolymerizing activity to provide more controlled microtubule depolymerization activity in extant cells.
format Online
Article
Text
id pubmed-9428548
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher The Royal Society
record_format MEDLINE/PubMed
spelling pubmed-94285482022-09-01 A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin Belsham, Hannah R. Alghamdi, Hanan M. Dave, Nikita Rathbone, Alexandra J. Wickstead, Bill Friel, Claire T. Open Biol Research The activity of a kinesin is largely determined by the approximately 350 residue motor domain, and this region alone is sufficient to classify a kinesin as a member of a particular family. The kinesin-13 family are a group of microtubule depolymerizing kinesins and are vital regulators of microtubule length. Kinesin-13s are critical to spindle assembly and chromosome segregation in both mitotic and meiotic cell division and play crucial roles in cilium length control and neuronal development. To better understand the evolution of microtubule depolymerization activity, we created a synthetic ancestral kinesin-13 motor domain. This phylogenetically inferred ancestral motor domain is the sequence predicted to have existed in the common ancestor of the kinesin-13 family. Here we show that the ancestral kinesin-13 motor depolymerizes stabilized microtubules faster than any previously tested depolymerase. This potent activity is more than an order of magnitude faster than the most highly studied kinesin-13, MCAK and allows the ancestral kinesin-13 to depolymerize doubly stabilized microtubules and cause internal breaks within microtubules. These data suggest that the ancestor of the kinesin-13 family was a ‘super depolymerizer’ and that members of the kinesin-13 family have evolved away from this extreme depolymerizing activity to provide more controlled microtubule depolymerization activity in extant cells. The Royal Society 2022-08-31 /pmc/articles/PMC9428548/ /pubmed/36043268 http://dx.doi.org/10.1098/rsob.220133 Text en © 2022 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, provided the original author and source are credited.
spellingShingle Research
Belsham, Hannah R.
Alghamdi, Hanan M.
Dave, Nikita
Rathbone, Alexandra J.
Wickstead, Bill
Friel, Claire T.
A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin
title A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin
title_full A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin
title_fullStr A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin
title_full_unstemmed A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin
title_short A synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin
title_sort synthetic ancestral kinesin-13 depolymerizes microtubules faster than any natural depolymerizing kinesin
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428548/
https://www.ncbi.nlm.nih.gov/pubmed/36043268
http://dx.doi.org/10.1098/rsob.220133
work_keys_str_mv AT belshamhannahr asyntheticancestralkinesin13depolymerizesmicrotubulesfasterthananynaturaldepolymerizingkinesin
AT alghamdihananm asyntheticancestralkinesin13depolymerizesmicrotubulesfasterthananynaturaldepolymerizingkinesin
AT davenikita asyntheticancestralkinesin13depolymerizesmicrotubulesfasterthananynaturaldepolymerizingkinesin
AT rathbonealexandraj asyntheticancestralkinesin13depolymerizesmicrotubulesfasterthananynaturaldepolymerizingkinesin
AT wicksteadbill asyntheticancestralkinesin13depolymerizesmicrotubulesfasterthananynaturaldepolymerizingkinesin
AT frielclairet asyntheticancestralkinesin13depolymerizesmicrotubulesfasterthananynaturaldepolymerizingkinesin
AT belshamhannahr syntheticancestralkinesin13depolymerizesmicrotubulesfasterthananynaturaldepolymerizingkinesin
AT alghamdihananm syntheticancestralkinesin13depolymerizesmicrotubulesfasterthananynaturaldepolymerizingkinesin
AT davenikita syntheticancestralkinesin13depolymerizesmicrotubulesfasterthananynaturaldepolymerizingkinesin
AT rathbonealexandraj syntheticancestralkinesin13depolymerizesmicrotubulesfasterthananynaturaldepolymerizingkinesin
AT wicksteadbill syntheticancestralkinesin13depolymerizesmicrotubulesfasterthananynaturaldepolymerizingkinesin
AT frielclairet syntheticancestralkinesin13depolymerizesmicrotubulesfasterthananynaturaldepolymerizingkinesin