Isolation and expression of a novel mitochondrial septin that interacts with CRMP/CRAM in the developing neurones

Background: Collapsin response mediator proteins (CRMPs) and CRAM belong to the unc‐33 gene family which is implicated in axon guidance and outgrowth during neural development. However, their exact roles remain largely unknown. To understand the molecular basis of CRMP/CRAM function, we have undertaken to identify CRMP/CRAM interacting proteins. Results: We have identified a novel mitochondrial septin (M‐septin) as one of the CRMP/CRAM interacting proteins from the developing rat brain. M‐septin is a major, alternatively spliced variant of the H5 gene in developing mouse brain and its expression is up‐regulated during the neuronal differentiation of embryonal carcinoma P19 cells. In COS‐7 cells, M‐septin is specifically localized to mitochondria whereas H5 is diffusely distributed to the perinuclear cytoplasm and plasma membranes. In contrast to H5, M‐septin induces the mitochondrial translocation of CRAM but not CRMP2. Finally, M‐Septin is found to be transiently translocated to mitochondria before the induction of the neurites and then dissociates from the mitochondria after neurite extension in P19 cells. Conclusions: Our results suggest that M‐septin has a role which is distinct from H5, and together with CRMP/CRAM, may play an important role in the neuronal differentiation and axon guidance through the control of mitochondrial function.