Polarity-regulating kinase partitioning-defective 1/microtubule affinity-regulating kinase 2 negatively regulates development of dendrites on hippocampal neurons.
Neurons are highly polarized cells that possess two morphologically and functionally different types of protrusions, axons and dendrites, that function in the transmission and reception of neural signals, respectively. A great deal of attention has been paid to the specification and guidance of axons, but the mechanism of dendrite development remains mostly unknown. We report here that a polarity-regulating kinase, partitioning-defective 1 (Par1b)/microtubule affinity-regulating kinase 2 (MARK2), specifically regulates development of dendrites in hippocampal neurons. Ectopic expression of Par1b/MARK2 shortens the length and decreases branching of dendrites without significant effects on axons. Knockdown of endogenous Par1b/MARK2 by RNA interference stimulates dendrite development. Wnt stimulation and Dishevelled expression, both of which are known to induce dendrite development, induced recruitment of Par1b/MARK2 to the membrane fraction. Expression of a Par1b/MARK2 mutant, that contains a myristoylation signal and accumulates exclusively in membranes, does not affect dendrite development. In addition, Par1b/MARK2 efficiently phosphorylated MAP2, which is localized mainly in dendrites. These results indicate that Par1b/MARK2 negatively regulates dendrite development through phosphorylation of MAP2.
Terabayashi
Takeshi
T
Laboratory of Intracellular Signaling, Institute for Protein Research, Osaka University, Suita, Osaka 565-0871, Japan.
Itoh
Tomohiko J
TJ
Yamaguchi
Hideki
H
Yoshimura
Yuta
Y
Funato
Yosuke
Y
Ohno
Shigeo
S
Miki
Hiroaki
H
D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003712:Dendrites / Q000502:physiology*; D004622:Embryo, Mammalian; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology*; D006801:Humans; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009154:Mutation / Q000502:physiology; D009474:Neurons / Q000166:cytology*; D015739:Nocodazole / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D012330:RNA, Double-Stranded / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection / Q000379:methods; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology; D051153:Wnt Proteins / Q000494:pharmacology; D060508:Wnt3 Protein
C489787:MAP2 protein, rat; D008869:Microtubule-Associated Proteins; D012330:RNA, Double-Stranded; D014404:Tubulin; D050257:Tubulin Modulators; D051153:Wnt Proteins; D060508:Wnt3 Protein; D049452:Green Fluorescent Proteins; C105549:MARK2 protein, rat; D017346:Protein Serine-Threonine Kinases; D015739:Nocodazole