Abstract：
:The molecular pathways controlling cerebellar Purkinje cell dendrite formation and maturation are poorly understood. The Purkinje cell degeneration (pcd) mutant mouse is characterized by mutations in Nna1, a gene discovered in an axonal regenerative context, but whose actual function in development and disease is unknown. We found abnormal development of Purkinje cell dendrites in postnatal pcd(Sid) mice and linked this deficit to a deletion mutation in exon 7 of Nna1. With single cell gene profiling and virus-based gene transfer, we analyzed a molecular pathway downstream to Nna1 underlying abnormal Purkinje cell dendritogenesis in pcd(Sid) mice. We discovered that mutant Nna1 dramatically increases intranuclear localization of lysyl oxidase propeptide, which interferes with NF-κB RelA signaling and microtubule-associated protein regulation of microtubule stability, leading to underdevelopment of Purkinje cell dendrites. These findings provide insight into Nna1's role in neuronal development and why its absence renders Purkinje cells more vulnerable.
journal_name
Neuronjournal_title
Neuronauthors
Li J,Gu X,Ma Y,Calicchio ML,Kong D,Teng YD,Yu L,Crain AM,Vartanian TK,Pasqualini R,Arap W,Libermann TA,Snyder EY,Sidman RLdoi
10.1016/j.neuron.2010.08.013subject
Has Abstractpub_date
2010-10-06 00:00:00pages
45-60issue
1eissn
0896-6273issn
1097-4199pii
S0896-6273(10)00623-9journal_volume
68pub_type
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