Autism spectrum disorder susceptibility gene TAOK2 affects basal dendrite formation in the neocortex.
How neurons develop their morphology is an important question in neurobiology. Here we describe a new pathway that specifically affects the formation of basal dendrites and axonal projections in cortical pyramidal neurons. We report that thousand-and-one-amino acid 2 kinase (TAOK2), also known as TAO2, is essential for dendrite morphogenesis. TAOK2 downregulation impairs basal dendrite formation in vivo without affecting apical dendrites. Moreover, TAOK2 interacts with Neuropilin 1 (Nrp1), a receptor protein that binds the secreted guidance cue Semaphorin 3A (Sema3A). TAOK2 overexpression restores dendrite formation in cultured cortical neurons from Nrp1(Sema-) mice, which express Nrp1 receptors incapable of binding Sema3A. TAOK2 overexpression also ameliorates the basal dendrite impairment resulting from Nrp1 downregulation in vivo. Finally, Sema3A and TAOK2 modulate the formation of basal dendrites through the activation of the c-Jun N-terminal kinase (JNK). These results delineate a pathway whereby Sema3A and Nrp1 transduce signals through TAOK2 and JNK to regulate basal dendrite development in cortical neurons.
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Froylan Calderon
FC
de Anda
Ana Lucia
AL
Rosario
Omer
O
Durak
Tracy
T
Tran
Johannes
J
Gräff
Konstantinos
K
Meletis
Damien
D
Rei
Takahiro
T
Soda
Ram
R
Madabhushi
David D
DD
Ginty
Alex L
AL
Kolodkin
Li-Huei
LH
Tsai
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000235:genetics* / Q000473:pathology; D003712:Dendrites / Q000502:physiology*; D015536:Down-Regulation / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D057809:HEK293 Cells; D006801:Humans; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D019579:Neocortex / Q000166:cytology* / Q000254:growth & development* / Q000473:pathology; D011247:Pregnancy; D017346:Protein Serine-Threonine Kinases; D051381:Rats
D017346:Protein Serine-Threonine Kinases; C122016:Taok2 protein, rat; D020930:MAP Kinase Kinase Kinases