Ablation of cytoskeletal scaffolding proteins, Band 4.1B and Whirlin, leads to cerebellar purkinje axon pathology and motor dysfunction

Purkinje neurons myelinated fibers require intact axonal cytoskeletal organization and axonal transport to effectively transmit neural signals. We show that proteins Band 4.1B and Whirlin cooperatively maintain axonal cytoskeletal integrity at the paranodal and juxtaparanodal regions, and their loss leads to axonal cytoskeletal disorganization and formation of swellings leading to axonal degeneration. AbstractThe cerebellar cortex receives neural information from other brain regions to allow fine motor coordination and motor learning. The primary output neurons from the cerebellum are the Purkinje neurons that transmit inhibitory responses to deep cerebellar nuclei through their myelinated axons. Altered morphological organization and electrical properties of the Purkinje axons lead to detrimental changes in locomotor activity often leading to cerebellar ataxias. Two cytoskeletal scaffolding proteins Band 4.1B (4.1B) and Whirlin (Whrn) have been previously shown to play independent roles in axonal domain organization and maintenance in myelinated axons in the spinal cord and sciatic nerves. Immunoblot analysis had indicated cerebellar expression for both 4.1B and Whrn; however, their subcellular localization and cerebellum ‐specific functions have not been characterized. Using4.1B andWhrn single and double mutant animals, we show that both proteins are expressed in common cellular compartments of the cerebellum and play cooperative roles in preservation of the integrity of ...
Source: Journal of Neuroscience Research - Category: Neuroscience Authors: Tags: RESEARCH ARTICLE Source Type: research