A neurodevelopmental TUBB2B β-tubulin mutation impairs Bim1 (yeast EB1)-dependent spindle positioning
Malformations of the human cerebral cortex can be caused by mutations in tubulins that associate to compose microtubules. Cerebral cortical folding relies on neuronal migration and on progenitor proliferation partly dictated by microtubule-dependent mitotic spindle positioning. A single amino acid c...
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doaj-2dab1dc0155641c58ba4f9c2c38f1fd12021-06-02T17:55:50ZengThe Company of BiologistsBiology Open2046-63902019-01-018110.1242/bio.038620038620A neurodevelopmental TUBB2B β-tubulin mutation impairs Bim1 (yeast EB1)-dependent spindle positioningEric Denarier0Carine Brousse1Abdoulaye Sissoko2Annie Andrieux3Cécile Boscheron4 Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000, Grenoble, France Institut National de la Transfusion Sanguine (INTS), F-75015 Paris, France Paris Descartes University, F-75006 Paris, France Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000, Grenoble, France Univ. Grenoble Alpes, Grenoble Institut des Neurosciences, GIN, F-38000, Grenoble, France Malformations of the human cerebral cortex can be caused by mutations in tubulins that associate to compose microtubules. Cerebral cortical folding relies on neuronal migration and on progenitor proliferation partly dictated by microtubule-dependent mitotic spindle positioning. A single amino acid change, F265L, in the conserved TUBB2B β-tubulin gene has been identified in patients with abnormal cortex formation. A caveat for studying this mutation in mammalian cells is that nine genes encode β-tubulin in human. Here, we generate a yeast strain expressing F265L tubulin mutant as the sole source of β-tubulin. The F265L mutation does not preclude expression of a stable β-tubulin protein which is incorporated into microtubules. However, impaired cell growth was observed at high temperatures along with altered microtubule dynamics and stability. In addition, F265L mutation produces a highly specific mitotic spindle positioning defect related to Bim1 (yeast EB1) dysfunction. Indeed, F265L cells display an abnormal Bim1 recruitment profile at microtubule plus-ends. These results indicate that the F265L β-tubulin mutation affects microtubule plus-end complexes known to be important for microtubule dynamics and for microtubule function during mitotic spindle positioning.http://bio.biologists.org/content/8/1/bio038620EB1MicrotubuleSpindle positioningTUBB2BYeast |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Eric Denarier Carine Brousse Abdoulaye Sissoko Annie Andrieux Cécile Boscheron |
spellingShingle |
Eric Denarier Carine Brousse Abdoulaye Sissoko Annie Andrieux Cécile Boscheron A neurodevelopmental TUBB2B β-tubulin mutation impairs Bim1 (yeast EB1)-dependent spindle positioning Biology Open EB1 Microtubule Spindle positioning TUBB2B Yeast |
author_facet |
Eric Denarier Carine Brousse Abdoulaye Sissoko Annie Andrieux Cécile Boscheron |
author_sort |
Eric Denarier |
title |
A neurodevelopmental TUBB2B β-tubulin mutation impairs Bim1 (yeast EB1)-dependent spindle positioning |
title_short |
A neurodevelopmental TUBB2B β-tubulin mutation impairs Bim1 (yeast EB1)-dependent spindle positioning |
title_full |
A neurodevelopmental TUBB2B β-tubulin mutation impairs Bim1 (yeast EB1)-dependent spindle positioning |
title_fullStr |
A neurodevelopmental TUBB2B β-tubulin mutation impairs Bim1 (yeast EB1)-dependent spindle positioning |
title_full_unstemmed |
A neurodevelopmental TUBB2B β-tubulin mutation impairs Bim1 (yeast EB1)-dependent spindle positioning |
title_sort |
neurodevelopmental tubb2b β-tubulin mutation impairs bim1 (yeast eb1)-dependent spindle positioning |
publisher |
The Company of Biologists |
series |
Biology Open |
issn |
2046-6390 |
publishDate |
2019-01-01 |
description |
Malformations of the human cerebral cortex can be caused by mutations in tubulins that associate to compose microtubules. Cerebral cortical folding relies on neuronal migration and on progenitor proliferation partly dictated by microtubule-dependent mitotic spindle positioning. A single amino acid change, F265L, in the conserved TUBB2B β-tubulin gene has been identified in patients with abnormal cortex formation. A caveat for studying this mutation in mammalian cells is that nine genes encode β-tubulin in human. Here, we generate a yeast strain expressing F265L tubulin mutant as the sole source of β-tubulin. The F265L mutation does not preclude expression of a stable β-tubulin protein which is incorporated into microtubules. However, impaired cell growth was observed at high temperatures along with altered microtubule dynamics and stability. In addition, F265L mutation produces a highly specific mitotic spindle positioning defect related to Bim1 (yeast EB1) dysfunction. Indeed, F265L cells display an abnormal Bim1 recruitment profile at microtubule plus-ends. These results indicate that the F265L β-tubulin mutation affects microtubule plus-end complexes known to be important for microtubule dynamics and for microtubule function during mitotic spindle positioning. |
topic |
EB1 Microtubule Spindle positioning TUBB2B Yeast |
url |
http://bio.biologists.org/content/8/1/bio038620 |
work_keys_str_mv |
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