title: Scaffold protein JLP is critical for CD40 signaling in B lymphocytes.
abstract: CD40 expression on the surface of B lymphocytes is essential for their biological function and fate decision. The engagement of CD40 with its cognate ligand, CD154, leads to a sequence of cellular events in B lymphocytes, including CD40 cytoplasmic translocation, a temporal and spatial organization of effector molecules, and a cascade of CD40-induced signal transduction. The JLP scaffold protein was expressed in murine B lymphocytes. Using B lymphocytes from jlp-deficient mice, we observed that JLP deficiency resulted in defective CD40 internalization upon CD154/CD40 engagement. Examination of interactions and co-localization among CD40, JLP, dynein, and Rab5 in B lymphocytes suggested that CD40 internalization is a process of JLP-mediated vesicle transportation that depends on Rab5 and dynein. JLP deficiency also diminished CD40-dependent activation of MAPK and JNK, but not NF-κB. Inhibiting vesicle transportation from the direction of cell periphery to the cell center by a dynein inhibitor (ciliobrevin D) impaired both CD154-induced CD40 internalization and CD40-dependent MAPK activities in B lymphocytes. Collectively, our data demonstrate a novel role of the JLP scaffold protein in the bridging of CD154-triggered CD40 internalization and CD40-dependent signaling in splenic B lymphocytes.
authors.affiliation: From the Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060, China, wanghuimingwhm@yahoo.com.
authors.forename: Hui-ming
authors.initials: HM
authors.lastname: Wang
authors.affiliation: From the Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yan
authors.affiliation: From the Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Yang
authors.affiliation: From the Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Cheng
authors.affiliation: From the Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
authors.forename: Juan
authors.initials: J
authors.lastname: Du
authors.affiliation: the Division of Molecular Cell Signaling, Department of Molecular and Cellular Biology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-0934, Japan.
authors.forename: Katsuji
authors.initials: K
authors.lastname: Yoshioka
authors.affiliation: the Department of Immunology, Faculty of Medicine, University of Manitoba, Winnipeg, Manitoba R3T 2N2, Canada, and.
authors.forename: Sam K P
authors.initials: SK
authors.lastname: Kung
authors.affiliation: From the Department of Nephrology, Renmin Hospital of Wuhan University, Wuhan 430060, China, ghxding@gmail.com.
authors.forename: Guo-hua
authors.initials: GH
authors.lastname: Ding
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000378:metabolism*; D015153:Blotting, Western; D019013:CD40 Antigens / Q000378:metabolism*; D023201:CD40 Ligand / Q000378:metabolism; D002478:Cells, Cultured; D004398:Dyneins / Q000378:metabolism; D004705:Endocytosis; D005260:Female; D005434:Flow Cytometry; D057809:HEK293 Cells; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019013:CD40 Antigens; C468928:Spag9 protein, mouse; D023201:CD40 Ligand; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D004398:Dyneins; D020696:rab5 GTP-Binding Proteins
keywords: Cell Signaling; Mitogen-activated Protein Kinase (MAPK); Receptor; Scaffold Protein; Trafficking