Siah regulation of Pard3A controls neuronal cell adhesion during germinal zone exit.
The brain's circuitry is established by directed migration and synaptogenesis of neurons during development. Although neurons mature and migrate in specific patterns, little is known about how neurons exit their germinal zone niche. We found that cerebellar granule neuron germinal zone exit is regulated by proteasomal degradation of Pard3A by the Seven in Absentia homolog (Siah) E3 ubiquitin ligase. Pard3A gain of function and Siah loss of function induce precocious radial migration. Time-lapse imaging using a probe to measure neuronal cell contact reveals that Pard3A promotes adhesive interactions needed for germinal zone exit by recruiting the epithelial tight junction adhesion molecule C to the neuronal cell surface. Our findings define a Siah-Pard3A signaling pathway that controls adhesion-dependent exit of neuronal progenitors or immature neurons from a germinal zone niche.
Department of Developmental Neurobiology, St. Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105, USA.
Jakub K
JK
Famulski
Niraj
N
Trivedi
Danielle
D
Howell
Yuan
Y
Yang
Yiai
Y
Tong
Richard
R
Gilbertson
David J
DJ
Solecki
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism*; D018797:Cell Cycle Proteins; D002460:Cell Line; D002465:Cell Movement; D016764:Cell Polarity; D002531:Cerebellum / Q000166:cytology* / Q000196:embryology / Q000378:metabolism*; D004285:Dogs; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D009024:Morphogenesis; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D015398:Signal Transduction; D013234:Stem Cells / Q000502:physiology; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism*; D054875:Ubiquitination
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D007136:Immunoglobulins; C486723:Jam3 protein, mouse; C115084:Pard3 protein, mouse; C484443:Siah1b protein, mouse; C533102:Siah2 protein, mouse; D044767:Ubiquitin-Protein Ligases