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| Subject Categories: Signal Transduction | Neuroscience |
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| The EMBO Journal
(2002) 21, 643–652, doi: 10.1093/emboj/21.4.643 |
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| CD40 is expressed and functional on neuronal cells |
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| Jun Tan1, Terrence Town1, Takashi Mori1, Demian Obregon1, Yajuan Wu1, Anthony DelleDonne1, Amyn Rojiani2, Fiona Crawford1, Richard A. Flavell3 and Mike Mullan1 |
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1 The Roskamp Institute, Department of Psychiatry, University of South Florida, 3515 East Fletcher Avenue, Tampa, FL 33613, USA 2 Department of Pathology, University of South Florida, 12901 Bruce B. Downs Boulevard, Tampa, FL 33612, USA 3 Howard Hughes Medical Institute, Yale University School of Medicine, 310 Cedar Street, Hew Haven, CT 06520, USA To whom correspondence should be addressed Jun Tan, jtan@hsc.usf.edu Received 19 June 2001; Revised 4 December 2001; Accepted 19 December 2001. |
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| Abstract |
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We show here that CD40 mRNA and protein are expressed by neuronal cells, and are increased in differentiated versus undifferentiated N2a and PC12 cells as measured by RT−PCR, western blotting and immunofluorescence staining. Additionally, immunohistochemistry reveals that neurons from adult mouse and human brain also express CD40 in situ. CD40 ligation results in a time-dependent increase in p44/42 MAPK activation in neuronal cells. Furthermore, ligation of CD40 opposes JNK phosphorylation and activity induced by NGF- removal from differentiated PC12 cells or serum withdrawal from primary cultured neurons. Importantly, CD40 ligation also protects neuronal cells from NGF- or serum withdrawal-induced injury and affects neuronal differentiation. Finally, adult mice deficient for the CD40 receptor demonstrate neuronal dysfunction as evidenced by decreased neurofilament isoforms, reduced Bcl-xL:Bax ratio, neuronal morphological change, increased DNA fragmentation, and gross brain abnormality. These changes occur with age, and are clearly evident at 16 months. Taken together, these data demonstrate a role of CD40 in neuronal development, maintenance and protection in vitro and in vivo. |
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| Keywords: apoptosis, CD40L, JNK, MAPK, neuron |
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