RanBPM contributes to TrkB signaling and regulates brain‐derived neurotrophic factor‐induced neuronal morphogenesis and survival

Abstract

J. Neurochem. (2010) 114, 110–121. Abstract Tropomyosin‐related kinase (Trk) B is a receptor tyrosine kinase for brain‐derived neurotrophic factor (BDNF) which plays a critical role in neuronal survival, differentiation and morphogenesis. Ran‐binding protein in the microtubule‐organizing center (RanBPM) is a cytosolic scaffold protein that has been shown to interact with protein‐tyrosine kinase receptor MET, Axl/Sky, and TrkA in addition to the pan‐neurotrophin receptor pan‐neurotrophin receptor 75 kDa. In this study, we report RanBPM is a novel TrkB‐interacting protein that contributes to BDNF‐induced MAPK and Akt activation together with neuronal morphogenesis and survival. Over‐expression of RanBPM in PC1210 cells (PC12 cells stably over‐expressing TrkB) can significantly enhance BDNF‐induced MAPK and Akt activation. Moreover, RanBPM can promote BDNF‐induced hippocampal neuronal morphogenesis and enhance BDNF‐mediated trophic effects after serum deprivation, while siRNA knock down of RanBPM in cells has the opposite effects. Together, these results suggest that RanBPM may modulate TrkB‐mediated downstream signaling and biological functions.

RanBPM is essential for mouse spermatogenesis and oogenesis

“…To date, only a few molecules have been shown to affect germ cell proliferation in the testis, the main one being the tyrosine kinase receptor Kit, which is also implicated in germ cell survival (Blume-Jensen et al, 2000;Kissel et al, 2000). RanBPM has been shown to interact with other tyrosine kinase receptors such as Met, TrkA (Ntrk1 -Mouse Genome Informatics) and TrkB (Ntrk2 -Mouse Genome Informatics) (Wang et al, 2002;Yin et al, 2010;Yuan et al, 2006). So, it would be of interest to investigate whether RanBPM does interact with Kit also and, if so, how it would affect its signaling property.…”

“…It binds the kelch-repeat protein muskelin affecting cell morphology (Valiyaveettil et al, 2008). In the immune system, it interacts with the 2-integrin LFA1 (lymphocyte function-associated antigen 1) (Denti et al, 2004), whereas in the nervous system it modulates axonal and neurite outgrowth by affecting the plexin-A receptors, the neural cell adhesion molecule L1 signaling and the neurotrophin receptor TrkB (Cheng et al, 2005;Murrin and Talbot, 2007;Togashi et al, 2006;Yin et al, 2010). In the embryonic neocortex, RanBPM is associated with the citron kinase (CITK), possibly affecting mitosis rate during production of pyramidal neurons (Chang et al, 2010).…”

LIM Kinase 1 (LIMK1) Interacts with Tropomyosin-related Kinase B (TrkB) and Mediates Brain-derived Neurotrophic Factor (BDNF)-induced Axonal Elongation

“…Cell Cultures and Transfections-HEK293 and PC12 cells were cultured as described previously (33). Briefly, HEK293 cells were cultured in Dulbecco's modified Eagle's medium (DMEM, Invitrogen) supplemented with 10% fetal bovine serum (FBS), 2 mM L-glutamine, and 100 units/ml penicillin/ streptomycin.…”

Insulin signalling in mushroom body neurons regulates feeding behaviour inDrosophilalarvae

“…Bai et al, 2003;Mikolajczyk et al, 2003;Menon et al, 2004;Brunkhorst et al, 2005;Hafizi et al, 2005;Haase et al, 2008;Atabakhsh et al, 2009;Gong et al, 2009;Kim et al, 2009;Chang et al, 2010) (reviewed by Murrin and Talbot, 2007). RanBPM expression in PC12 cells promotes TrkB-dependent activation of the serine-threonine kinase Akt, a target of insulin signalling (Yin et al, 2010).…”