APC functions at the centrosome to stimulate microtubule growth

Christina Lui, Cahora Ashton, Manisha Sharma, Mariana G. Brocardo, Beric R. Henderson

Research output: Contribution to journalArticleResearchpeer-review

Abstract

The adenomatous polyposis coli (APC) tumor suppressor is multi-functional. APC is known to localize at the centrosome, and in mitotic cells contributes to formation of the mitotic spindle. To test whether APC contributes to nascent microtubule (MT) growth at interphase centrosomes, we employed MT regrowth assays in U2OS cells to measure MT assembly before and after nocodazole treatment and release. We showed that siRNA knockdown of full-length APC delayed both initial MT aster formation and MT elongation/regrowth. In contrast, APC-mutant SW480 cancer cells displayed a defect in MT regrowth that was unaffected by APC knockdown, but which was rescued by reconstitution of full-length APC. Our findings identify APC as a positive regulator of centrosome MT initial assembly and suggest that this process is disrupted by cancer mutations. We confirmed that full-length APC associates with the MT-nucleation factor γ-tubulin, and found that the APC cancer-truncated form (1-1309) also bound to γ-tubulin through APC amino acids 1-453. While binding to γ-tubulin may help target APC to the site of MT nucleation complexes, additional C-terminal sequences of APC are required to stimulate and stabilize MT growth.

LanguageEnglish
Pages39-47
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
Volume70
DOIs
Publication statusPublished - 1 Jan 2016
Externally publishedYes

Fingerprint

Centrosome
Adenomatous Polyposis Coli
Tubulin
Microtubules
Nucleation
Growth
Nocodazole
Small Interfering RNA
Tumors
Elongation
Assays
Cells
Amino Acids
Defects
Neoplasms
Spindle Apparatus
Interphase

Cite this

Lui, Christina ; Ashton, Cahora ; Sharma, Manisha ; Brocardo, Mariana G. ; Henderson, Beric R. / APC functions at the centrosome to stimulate microtubule growth. In: International Journal of Biochemistry and Cell Biology. 2016 ; Vol. 70. pp. 39-47.
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APC functions at the centrosome to stimulate microtubule growth. / Lui, Christina; Ashton, Cahora; Sharma, Manisha; Brocardo, Mariana G.; Henderson, Beric R.

In: International Journal of Biochemistry and Cell Biology, Vol. 70, 01.01.2016, p. 39-47.

Research output: Contribution to journalArticleResearchpeer-review

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