Phosphorylation of Rab5a protein by protein kinase Cϵ is crucial for T-cell migration

• Main Authors: Ong, Seow Theng, Freeley, Michael, Skubis-Zegadło, Joanna, Fazil, Mobashar Hussain Urf Turabe, Kelleher, Dermot, Fresser, Friedrich, Baier, Gottfried, Verma, Navin Kumar, Long, Aideen
• Other Authors: Lee Kong Chian School of Medicine (LKCMedicine)
• Format: Article
• Language: English
• Published: 2014
• Subjects: DRNTU::Science::Biological sciences
• Online Access: https://hdl.handle.net/10356/105810; http://hdl.handle.net/10220/20966
• Institution: Nanyang Technological University

Rab GTPases control membrane traffic and receptor-mediated endocytosis. Within this context, Rab5a plays an important role in the spatial regulation of intracellular transport and signal transduction processes. Here, we report a previously uncharacterized role for Rab5a in the regulation of T-cell motility. We show that Rab5a physically associates with protein kinase C ε (PKC ε ) in migrating T-cells. Following stimulation of T- cells through the integrin LFA-1 or the chemokine receptor CXCR4, Rab5a is phosphorylated on a N-terminal T7 site by PKC ε . Both Rab5a and PKC ε dynamically interact at the centrosomal region of migrating cells, and PKC ε -mediated phosphorylation on T7 regulates Rab5a trafficking to the cell leading edge. Further, we demonstrate that Rab5a T7 phosphorylation is functionally necessary for Rac1 activation, actin rearrangement and T- cell motility. We present a novel mechanism by which a PKC ε -Rab5a-Rac1 axis regulates cytoskeleton remodelling and T-cell migration, both of which are central for the adaptive immune response.