ASPP2 binds Par-3 and controls the polarity and proliferation of neural progenitors during CNS development.
Cell polarity plays a key role in the development of the central nervous system (CNS). Interestingly, disruption of cell polarity is seen in many cancers. ASPP2 is a haplo-insufficient tumor suppressor and an activator of the p53 family. In this study, we show that ASPP2 controls the polarity and proliferation of neural progenitors in vivo, leading to the formation of neuroblastic rosettes that resemble primitive neuroepithelial tumors. Consistent with its role in cell polarity, ASPP2 influences interkinetic nuclear migration and lamination during CNS development. Mechanistically, ASPP2 maintains the integrity of tight/adherens junctions. ASPP2 binds Par-3 and controls its apical/junctional localization without affecting its expression or Par-3/aPKC lambda binding. The junctional localization of ASPP2 and Par-3 is interdependent, suggesting that they are prime targets for each other. These results identify ASPP2 as a regulator of Par-3, which plays a key role in controlling cell proliferation, polarity, and tissue organization during CNS development.
Sottocornola
Roberta
R
Ludwig Institute for Cancer Research, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Headington, Oxford OX3 7DQ, UK.
Royer
Christophe
C
Vives
Virginie
V
Tordella
Luca
L
Zhong
Shan
S
Wang
Yihua
Y
Ratnayaka
Indrika
I
Shipman
Mark
M
Cheung
Amanda
A
Gaston-Massuet
Carles
C
Ferretti
Patrizia
P
Molnár
Zoltán
Z
Lu
Xin
X
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000502:physiology*; D018797:Cell Cycle Proteins; D016764:Cell Polarity / Q000502:physiology; D049109:Cell Proliferation; D002490:Central Nervous System / Q000002:abnormalities / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019579:Neocortex / Q000002:abnormalities / Q000196:embryology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D011247:Pregnancy; D011485:Protein Binding; D012160:Retina / Q000002:abnormalities / Q000196:embryology; D019108:Tight Junctions / Q000378:metabolism / Q000648:ultrastructure; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
D048868:Adaptor Proteins, Signal Transducing; D015815:Cell Adhesion Molecules; D018797:Cell Cycle Proteins; D017931:DNA Primers; C115084:Pard3 protein, mouse; C511437:Trp53bp2 protein, mouse; D025521:Tumor Suppressor Proteins