title: Maintenance of dendritic spine morphology by partitioning-defective 1b through regulation of microtubule growth.
abstract: Dendritic spines are postsynaptic structures that receive excitatory synaptic input from presynaptic terminals. Actin and its regulatory proteins play a central role in morphogenesis of dendritic spines. In addition, recent studies have revealed that microtubules are indispensable for the maintenance of mature dendritic spine morphology by stochastically invading dendritic spines and regulating dendritic localization of p140Cap, which is required for actin reorganization. However, the regulatory mechanisms of microtubule dynamics remain poorly understood. Partitioning-defective 1b (PAR1b), a cell polarity-regulating serine/threonine protein kinase, is thought to regulate microtubule dynamics by inhibiting microtubule binding of microtubule-associated proteins. Results from the present study demonstrated that PAR1b participates in the maintenance of mature dendritic spine morphology in mouse hippocampal neurons. Immunofluorescent analysis revealed PAR1b localization in the dendrites, which was concentrated in dendritic spines of mature neurons. PAR1b knock-down cells exhibited decreased mushroom-like dendritic spines, as well as increased filopodia-like dendritic protrusions, with no effect on the number of protrusions. Live imaging of microtubule plus-end tracking proteins directly revealed decreases in distance and duration of microtubule growth following PAR1b knockdown in a neuroblastoma cell line and in dendrites of hippocampal neurons. In addition, reduced accumulation of GFP-p140Cap in dendritic protrusions was confirmed in PAR1b knock-down neurons. In conclusion, the present results suggested a novel function for PAR1b in the maintenance of mature dendritic spine morphology by regulating microtubule growth and the accumulation of p140Cap in dendritic spines.
authors.affiliation: Department of Molecular Biology, Yokohama City University Graduate School of Medical Science, Kanazawa-ku, Yokohama 236-0004, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Hayashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Suzuki
authors.forename: Syu-ichi
authors.initials: S
authors.lastname: Hirai
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kurihara
authors.forename: Casper C
authors.initials: CC
authors.lastname: Hoogenraad
authors.forename: Shigeo
authors.initials: S
authors.lastname: Ohno
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000235:genetics*; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000502:physiology; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D006624:Hippocampus / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D017346:Protein Serine-Threonine Kinases / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D018797:Cell Cycle Proteins; C122043:Mark2 protein, mouse; D017346:Protein Serine-Threonine Kinases