The mammalian Golgi regulates numb signaling in asymmetric cell division by releasing ACBD3 during mitosis.
Mammalian neural progenitor cells divide asymmetrically to self-renew and produce a neuron by segregating cytosolic Numb proteins primarily to one daughter cell. Numb signaling specifies progenitor over neuronal fates but, paradoxically, also promotes neuronal differentiation. Here we report that ACBD3 is a Numb partner in cell-fate specification. ACBD3 and Numb proteins interact through an essential Numb domain, and the respective loss- and gain-of-function mutant mice share phenotypic similarities. Interestingly, ACBD3 associates with the Golgi apparatus in neurons and interphase progenitor cells but becomes cytosolic after Golgi fragmentation during mitosis, when Numb activity is needed to distinguish the two daughter cells. Accordingly, cytosolic ACBD3 can act synergistically with Numb to specify cell fates, and its continuing presence during the progenitor cell cycle inhibits neuron production. We propose that Golgi fragmentation and reconstitution during cell cycle differentially regulate Numb signaling through changes in ACBD3 subcellular distribution and represent a mechanism for coupling cell-fate specification and cell-cycle progression.
Zhou
Yan
Y
Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA.
Atkins
Joshua B
JB
Rompani
Santiago B
SB
Bancescu
Daria L
DL
Petersen
Petur H
PH
Tang
Haiyan
H
Zou
Kaiyong
K
Stewart
Sinead B
SB
Zhong
Weimin
W
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D030801:Animals, Genetically Modified; D002455:Cell Division; D019070:Cell Lineage; D003600:Cytosol / Q000737:chemistry; D004330:Drosophila; D004622:Embryo, Mammalian / Q000378:metabolism; D004625:Embryo, Nonmammalian; D047108:Embryonic Development / Q000235:genetics; D006056:Golgi Apparatus / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008938:Mitosis; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology; D010641:Phenotype; D017434:Protein Structure, Tertiary; D011963:Receptors, GABA-A / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013234:Stem Cells / Q000166:cytology
C486730:Acbd3 protein, mouse; D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C106293:Numb protein, mouse; D011963:Receptors, GABA-A