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Mutations in the microtubule-associated protein MAP11 (C7orf43) cause microcephaly in humans and zebrafish.


ABSTRACT: Microtubule associated protein 11 (MAP11, previously termed C7orf43) encodes a highly conserved protein whose function is unknown. Through genome-wide linkage analysis combined with whole exome sequencing, we demonstrate that human autosomal recessive primary microcephaly is caused by a truncating mutation in MAP11. Moreover, homozygous MAP11-orthologue CRISPR/Cas9 knock-out zebrafish presented with microcephaly and decreased neuronal proliferation, recapitulating the human phenotype. We demonstrate that MAP11 is ubiquitously transcribed with high levels in brain and cerebellum. Immunofluorescence and co-immunoprecipitation studies in SH-SY5Y cells showed that MAP11 associates with mitotic spindles, co-localizing and physically associating with ?-tubulin during mitosis. MAP11 expression precedes ?-tubulin in gap formation of cell abscission at the midbody and is co-localized with PLK1, a key regulator of cytokinesis, at the edges of microtubule extensions of daughter cells post cytokinesis abscission, implicating a role in mitotic spindle dynamics and in regulation of cell abscission during cytokinesis. Finally, lentiviral-mediated silencing of MAP11 diminished SH-SY5Y cell viability, reducing proliferation rather than affecting apoptosis. Thus, MAP11 encodes a microtubule-associated protein that plays a role in spindle dynamics and cell division, in which mutations cause microcephaly in humans and zebrafish.

SUBMITTER: Perez Y 

PROVIDER: S-EPMC6391606 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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Mutations in the microtubule-associated protein MAP11 (C7orf43) cause microcephaly in humans and zebrafish.

Perez Yonatan Y   Bar-Yaacov Reut R   Kadir Rotem R   Wormser Ohad O   Shelef Ilan I   Birk Ohad S OS   Flusser Hagit H   Birnbaum Ramon Y RY  

Brain : a journal of neurology 20190301 3


Microtubule associated protein 11 (MAP11, previously termed C7orf43) encodes a highly conserved protein whose function is unknown. Through genome-wide linkage analysis combined with whole exome sequencing, we demonstrate that human autosomal recessive primary microcephaly is caused by a truncating mutation in MAP11. Moreover, homozygous MAP11-orthologue CRISPR/Cas9 knock-out zebrafish presented with microcephaly and decreased neuronal proliferation, recapitulating the human phenotype. We demonst  ...[more]

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