TY - JOUR
T1 - Regulation of neuronal morphogenesis and positioning by ubiquitin-specific proteases in the cerebellum e0117076
AU - Anckar, Julius
AU - Bonni, Azad
N1 - Publisher Copyright:
© 2015 Anckar Bonni.
PY - 2015/1/21
Y1 - 2015/1/21
N2 - Ubiquitin signaling mechanisms play fundamental roles in the cell-intrinsic control of neuronal morphogenesis and connectivity in the brain. However, whereas specific ubiquitin ligases have been implicated in key steps of neural circuit assembly, the roles of ubiquitinspecific proteases (USPs) in the establishment of neuronal connectivity have remained unexplored. Here, we report a comprehensive analysis of USP family members in granule neuron morphogenesis and positioning in the rodent cerebellum. We identify a set of 32 USPs that are expressed in granule neurons. We also characterize the subcellular localization of the 32 USPs in granule neurons using a library of expression plasmids encoding GFP-USPs. In RNAi screens of the 32 neuronally expressed USPs, we uncover novel functions for USP1, USP4, and USP20 in the morphogenesis of granule neuron dendrites and axons and we identify a requirement for USP30 and USP33 in granule neuron migration in the rodent cerebellar cortex in vivo. These studies reveal that specific USPs with distinct spatial localizations harbor key functions in the control of neuronal morphogenesis and positioning in the mammalian cerebellum, with important implications for our understanding of the cell-intrinsic mechanisms that govern neural circuit assembly in the brain.
AB - Ubiquitin signaling mechanisms play fundamental roles in the cell-intrinsic control of neuronal morphogenesis and connectivity in the brain. However, whereas specific ubiquitin ligases have been implicated in key steps of neural circuit assembly, the roles of ubiquitinspecific proteases (USPs) in the establishment of neuronal connectivity have remained unexplored. Here, we report a comprehensive analysis of USP family members in granule neuron morphogenesis and positioning in the rodent cerebellum. We identify a set of 32 USPs that are expressed in granule neurons. We also characterize the subcellular localization of the 32 USPs in granule neurons using a library of expression plasmids encoding GFP-USPs. In RNAi screens of the 32 neuronally expressed USPs, we uncover novel functions for USP1, USP4, and USP20 in the morphogenesis of granule neuron dendrites and axons and we identify a requirement for USP30 and USP33 in granule neuron migration in the rodent cerebellar cortex in vivo. These studies reveal that specific USPs with distinct spatial localizations harbor key functions in the control of neuronal morphogenesis and positioning in the mammalian cerebellum, with important implications for our understanding of the cell-intrinsic mechanisms that govern neural circuit assembly in the brain.
UR - http://www.scopus.com/inward/record.url?scp=84921807211&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0117076
DO - 10.1371/journal.pone.0117076
M3 - Article
C2 - 25607801
AN - SCOPUS:84921807211
SN - 1932-6203
VL - 10
JO - PloS one
JF - PloS one
IS - 1
M1 - e0117076
ER -