Characterizing NOS1AP in the Rodent Cerebellum

Abstract

Nitric Oxide Synthase 1 adaptor protein (NOS1AP) has been implicated in several diseases in the CNS. NOS1AP functions as an adaptor protein that can bind to several proteins, including neuronal nitric oxide synthase (nNOS). Mice lacking NOS1AP show significant defects in balance and gait, consistent with a role for NOS1AP in the cerebellum. Although NOS1AP mutant mice show no gross cerebellar defects, using isoform specific antibodies combined with different NOS1AP mutant mice reveals that NOS1APa is expressed in parvalbumin positive interneurons in the outer molecular layer, and is necessary to maintain nNOS localization in these neurons. Unlike NOS1APa, NOS1APc is expressed in Bergmann glia, and is necessary for climbing fiber distribution. Further, quantitative mass spectrometry analysis reveals that loss of NOS1AP influences the expression of proteins involved in GABAergic signaling, highlighting the importance of NOS1AP proteins in maintaining excitatory/inhibitory homeostasis within the cerebellum which is necessary for normal gait.