Regulation of neuronal morphogenesis and positioning by ubiquitin-specific proteases in the cerebellum e0117076

Julius Anckar, Azad Bonni

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere117076
JournalPloS one
Volume10
Issue number1
DOIs
StatePublished - Jan 21 2015

Fingerprint

Dive into the research topics of 'Regulation of neuronal morphogenesis and positioning by ubiquitin-specific proteases in the cerebellum e0117076'. Together they form a unique fingerprint.

Cite this