ZFIN ID: ZDB-PUB-190205-7
Mutations in the microtubule-associated protein MAP11 (C7orf43) cause microcephaly in humans and zebrafish
Perez, Y., Bar-Yaacov, R., Kadir, R., Wormser, O., Shelef, I., Birk, O.S., Flusser, H., Birnbaum, R.Y.
Date: 2019
Source: Brain : a journal of neurology   142(3): 574-585 (Journal)
Registered Authors: Birnbaum, Ramon
Keywords: none
MeSH Terms:
  • Animals
  • Cell Cycle Proteins/metabolism
  • Child
  • Child, Preschool
  • Cytokinesis
  • Disease Models, Animal
  • Female
  • HeLa Cells
  • Humans
  • Male
  • Microcephaly/etiology*
  • Microcephaly/genetics*
  • Microcephaly/metabolism
  • Microtubule-Associated Proteins/genetics*
  • Microtubule-Associated Proteins/metabolism
  • Microtubules/genetics
  • Mitosis
  • Mutation
  • Protein-Serine-Threonine Kinases/metabolism
  • Proto-Oncogene Proteins/metabolism
  • Spindle Apparatus/genetics
  • Tubulin/genetics
  • Tubulin/metabolism
  • Zebrafish/metabolism
  • Zebrafish Proteins/metabolism
PubMed: 30715179 Full text @ Brain
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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 α-tubulin during mitosis. MAP11 expression precedes α-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.
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