CRMP5 (Collapsin Response Mediator Protein 5) Regulates Dendritic Development and Synaptic Plasticity in the Cerebellar Purkinje Cells

Abstract

Collapsin response mediator protein 5 (CRMP5) is one of the CRMP members that expresses abundantly in the developing brain. To examine the in vivo function of CRMP5, we generated crmp5-deficient (crmp5 Ϫ/Ϫ ) mice. Anti-calbindin immunofluorescence studies of crmp5 Ϫ/Ϫ mice revealed aberrant dendrite morphology; specifically, a decrease in the size of soma and diameter of primary dendrite of the cerebellar Purkinje cells at postnatal day 21 (P21) and P28, but not at P14. Coincidentally, CRMP5 is detected in Purkinje cells at P21 and P28 from crmp5 ϩ/Ϫ mice. In cerebellar slices of crmp5 Ϫ/Ϫ mice, the induction of long-term depression of excitatory synaptic transmission between parallel fibers and Purkinje cells was deficient. Given that brain-derived neurotrophic factor (BDNF) plays major roles in dendritic development, we tried to elucidate the possible roles of CRMP5 in BDNF signaling. The effect of BDNF to induce dendritic branching was markedly attenuated in cultured crmp5 Ϫ/Ϫ neurons. Furthermore, CRMP5 was tyrosine phosphorylated when coexpressed with neurotrophic tyrosine kinase receptor type 2 (TrkB), a receptor for BDNF, in HEK293T cells. These findings suggest that CRMP5 is involved in the development, maintenance and synaptic plasticity of Purkinje cells.

Phosphorylation of CRMP2 (Collapsin Response Mediator Protein 2) Is Involved in Proper Dendritic Field Organization

“…CRMPs are involved in cell migration , axonal guidance (Goshima et al, 1995;Arimura et al, 2005;Uchida et al, 2005;Yoshimura et al, 2005), dendritic spine development (Yamashita et al, 2007) and synaptic plasticity (Yamashita et al, 2011) through its phosphorylation. In Semaphorin3A (Sema3A) signaling, CRMP2 is phosphorylated by Cdk5 at Ser522.…”

Collapsin Response Mediator Protein 5 (CRMP5) Induces Mitophagy, Thereby Regulating Mitochondrion Numbers in Dendrites

“…Another study has reported that it exerts a role in the regulation of filopodial dynamics and growth cone development (25). The results obtained recently with CRMP5-deficient mice stress the role of CRMP5 in the development and synaptic plasticity of cerebellar Purkinje cells (26). We reported CRMP5 inhibition of neurite outgrowth, especially at the dendritic level, by forming a complex with tubulin and microtubule-associated protein 2 (MAP2).…”

Mapping CRMP3 domains involved in dendrite morphogenesis and voltage-gated calcium channel regulation

“…CRMP5 also interacts with tubulin to remodel the function of CRMP2 (Brot et al, 2010). However, perhaps the most significant conceptual advance come from our CRMP5 and CRMP1 gene targeting in mice: these two members of the CRMP family, which are distributed in many regions of the CNS, including the cortex, hippocampus and cerebellum, appear to play key integrative roles in neuronal migration, learning and memory (Bretin et al, 2005;Charrier et al, 2006;Yamashita et al, 2006) and in neurological diseases (Camdessanche et al, 2012;Yamashita et al, 2011).…”