title: Regulation of microtubule stability and organization by mammalian Par3 in specifying neuronal polarity.
abstract: Polarization of mammalian neurons with a specified axon requires precise regulation of microtubule and actin dynamics in the developing neurites. Here we show that mammalian partition defective 3 (mPar3), a key component of the Par polarity complex that regulates the polarization of many cell types including neurons, directly regulates microtubule stability and organization. The N-terminal portion of mPar3 exhibits strong microtubule binding, bundling, and stabilization activity, which can be suppressed by its C-terminal portion via an intramolecular interaction. Interestingly, the intermolecular oligomerization of mPar3 is able to relieve the intramolecular interaction and thereby promote microtubule bundling and stabilization. Furthermore, disruption of this microtubule regulatory activity of mPar3 impairs its function in axon specification. Together, these results demonstrate a role for mPar3 in directly regulating microtubule organization that is crucial for neuronal polarization.
authors.affiliation: Developmental Biology Program, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10065, USA. chens12@mskcc.org
authors.forename: She
authors.initials: S
authors.lastname: Chen
authors.forename: Jia
authors.initials: J
authors.lastname: Chen
authors.forename: Hang
authors.initials: H
authors.lastname: Shi
authors.forename: Michelle
authors.initials: M
authors.lastname: Wei
authors.forename: David R
authors.initials: DR
authors.lastname: Castaneda-Castellanos
authors.forename: Ronald S
authors.initials: RS
authors.lastname: Bultje
authors.forename: Xin
authors.initials: X
authors.lastname: Pei
authors.forename: Arnold R
authors.initials: AR
authors.lastname: Kriegstein
authors.forename: Mingjie
authors.initials: M
authors.lastname: Zhang
authors.forename: Song-Hai
authors.initials: SH
authors.lastname: Shi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D001369:Axons / Q000378:metabolism; D019556:COS Cells; D015815:Cell Adhesion Molecules / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D018797:Cell Cycle Proteins; D016764:Cell Polarity; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D031541:Fluorescence Resonance Energy Transfer; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D047468:Immunoprecipitation; D051379:Mice; D008870:Microtubules / Q000737:chemistry / Q000502:physiology*; D008969:Molecular Sequence Data; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; C115084:Pard3 protein, mouse; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins