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

Yonatan Perez, Reut Bar-Yaacov, Rotem Kadir, Ohad Wormser, Ilan Shelef, Ohad S. Birk, Hagit Flusser, Ramon Y. Birnbaum

نتاج البحث: نشر في مجلةمقالةمراجعة النظراء

ملخص

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.

اللغة الأصليةإنجليزيّة أمريكيّة
الصفحات (من إلى)574-585
عدد الصفحات12
دوريةBrain
مستوى الصوت142
رقم الإصدار3
المعرِّفات الرقمية للأشياء
حالة النشرنُشِر - 1 مارس 2019

All Science Journal Classification (ASJC) codes

  • !!Clinical Neurology

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