Investigating the Effects of Atlastin-1 on Spastin and REEP1 Using Primary Cultured Neurons from Mice with Motor Neuron Disease

Abstract

Disruption in axonal transport is a common cause of motor neuron degeneration and is associated with many neurological disorders including the hereditary spastic paraplegias (HSP’s). HSP’s are a group of inherited disorders characterized by weakness and spasticity in the lower limbs that pathologically lead to retrograde degeneration of corticospinal neurons. Over half of all autosomal dominant cases of HSP are caused by mutations in spastin (SPG4), atlastin (SPG3A), and receptor expression enhancing protein (REEP1). These proteins co-localize and bind together in the endoplasmic reticulum and are directly involved in the coordination of ER shaping and microtubule dynamics in corticospinal neurons (Figure 1). The collaboration of these three HSP proteins suggests that mutations may cause impairments in the relationship between ER tubules and microtubule cytoskeleton. This study used primary cortical neuron cultures from adult knockout atlastin mice in an attempt to investigate the consequences of reducing atlastin-1 protein levels in mouse models.