Biomedical Research Education & Training
Faculty Member

Carter, Bruce D., Ph.D.
Professor of Biochemistry

Lab Url: http://www.brucecarterlab.com/index.html

Phone Number: (615) 936-3041

Email Address: bruce.carter@vanderbilt.edu

Carter, Bruce's picture
Academic history
B.S., Alma College, Alma, MI
Ph.D., University of Michigan, Ann Arbor, MI
Postdoc, Max Planck Inst. for Psychiatry, Munich, Germany
Postdoc, Cornell Univ. Med. School, New York, NY

Office Address   Mailing Address

625 Light Hall

625 Light Hall 0146


Research Keywords
neurotrophins, signaling proteins, apoptosis, transcription factor, receptor, nerve growth factor, NGF, cell death, myelin, neuron, schwann cell, glia ,Apoptosis,Biochemistry,Developmental biology,Mouse,Neuroscience,Post-transcriptional modification,Receptor,Signal transduction

Research Specialty
Molecular mechanisms of neurotrophin signaling

Research Description
I. Molecular mechanisms of neurotrophin signaling ?Our lab studies the signaling mechanisms regulating neuronal survival. Programmed cell death in the nervous system is a naturally occurring process in mammalian development; however, abnormal apoptosis is the basis for many neuropathologies, e.g. Alzheimer's and Parkinson's disease and ischemic injury. The delicate balance between neuronal survival and death is regulated, in part, by a family of growth factors referred to as the neurotrophins. The target tissues to which the neurons project produce members of this family of trophic factors. The neurotrophins promote neuronal survival and differentiation through binding to the Trks, a family of tyrosine kinase receptors, and induce apoptosis through a 75kD receptor, p75. While significant progress has been made in elucidating the mechanisms by which the Trks promote survival, much less is known about how p75 induces cell death. We recently discovered that pro-death ligands promote p75 cleavage by ??secretase, which releases a transcription factor, NRIF, to enter the nucleus. This process is required for the receptor's apoptotic signal.This research will reveal the mechanisms underlying normal mammalian neural development and function. Moreover, understanding the regulation of neural cell survival is essential for developing therapeutic strategies for neuropathologies involving apoptosis, which include many diseases and nerve lesions.

II.Molecular mechanisms of myelin formation?The other area of research in the lab is to elucidate the mechanism by which myelin forms. Myelin is a multilamellar structure that ensheaths axons and allows for the rapid conduction of electrical signals, acts as a protective barrier for axons, regulates regeneration and provides trophic support for neurons. This structure is produced by Schwann cells in the peripheral nervous system and oligodendrocytes in the CNS. The formation of peripheral myelin during development is initiated by yet to be identified signals from the axon with which the Schwann cells are associated. The overall objective of this project is to elucidate the mechanisms regulating the formation of this essential neural structure. We found that activation of the transcription factor NF-?B in Schwann cells is essential for their differentiation into a myelinating phenotype and are currently investigating the up stream activator of NF-?B and what the downstream targets are.The formation of myelin is critical for the normal function of the mammalian nervous system. Disruptions in myelination during development lead to a variety of muscular dystrophies, in particular Charcot-Marie-Tooth disease, and degeneration of myelin in adults can lead to disabling pathologies such as Multiple Sclerosis and Guillian Barre Syndrome. In addition, myelin is a key regulator of nerve regeneration, preventing it in the CNS and promoting it in the periphery. Therefore, understanding how this specialized structure forms may reveal mechanisms underlying the etiology of a number pathologies as well as potential points for therapeutic intervention.

Publications
Limpert, AS, Bai, S, Narayan, M, Wu, J, Yoon, SO, Carter, BD, Lu, QR. NF-??B forms a complex with the chromatin remodeler BRG1 to regulate Schwann cell differentiation. J Neurosci, 33(6), 2388-97, 2013

Schlebach, JP, Peng, D, Kroncke, BM, Mittendorf, KF, Narayan, M, Carter, BD, Sanders, CR. Reversible Folding of Human Peripheral Myelin Protein 22, a Tetraspan Membrane Protein. Biochemistry, 2013

Wei, C, Thatcher, EJ, Olena, AF, Cha, DJ, Perdigoto, AL, Marshall, AF, Carter, BD, Broadie, K, Patton, JG. miR-153 regulates SNAP-25, synaptic transmission, and neuronal development. PLoS One, 8(2), e57080, 2013

Benesh, AE, Fleming, JT, Chiang, C, Carter, BD, Tyska, MJ. Expression and localization of myosin-1d in the developing nervous system. Brain Res, 1440, 9-22, 2012

Scheib, JL, Sullivan, CS, Carter, BD. Jedi-1 and MEGF10 Signal Engulfment of Apoptotic Neurons through the Tyrosine Kinase Syk. J Neurosci, 32(38), 13022-31, 2012

Tep, C, Kim, ML, Opincariu, LI, Limpert, AS, Chan, JR, Appel, B, Carter, BD, Yoon, SO. Brain-derived neurotrophic factor (BDNF) induces polarized signaling of small GTPase (Rac1) protein at the onset of Schwann cell myelination through partitioning-defective 3 (Par3) protein. J Biol Chem, 287(2), 1600-8, 2012

Astuti, D, Ricketts, CJ, Chowdhury, R, McDonough, MA, Gentle, D, Kirby, G, Schlisio, S, Kenchappa, RS, Carter, BD, Kaelin, WG, Ratcliffe, PJ, Schofield, CJ, Latif, F, Maher, ER. Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility. Endocr Relat Cancer, 18(1), 73-83, 2011 PMCID:3006001

Duggan, KC, Hermanson, DJ, Musee, J, Prusakiewicz, JJ, Scheib, JL, Carter, BD, Banerjee, S, Oates, JA, Marnett, LJ. (R)-Profens are substrate-selective inhibitors of endocannabinoid oxygenation by COX-2. Nat Chem Biol, 7(11), 803-9, 2011

Perdigoto, AL, Chaudhry, N, Barnes, GN, Filbin, MT, Carter, BD. A novel role for PTEN in the inhibition of neurite outgrowth by myelin-associated glycoprotein in cortical neurons. Mol Cell Neurosci, 46(1), 235-44, 2011

Carter, BD. Degeneration keeps axons on the straight and narrow. Nat Neurosci, 13(5), 526-8, 2010

Carter, BD, Feng, N, Paolocci, N. The p75 neurotrophin receptor, semaphorins, and sympathetic traffic in the heart. Am J Physiol Heart Circ Physiol, 298(6), H1633-6, 2010 PMCID:2886656

Kenchappa, RS, Tep, C, Korade, Z, Urra, S, Bronfman, FC, Yoon, SO, Carter, BD. p75 neurotrophin receptor-mediated apoptosis in sympathetic neurons involves a biphasic activation of JNK and up-regulation of tumor necrosis factor-alpha-converting enzyme/ADAM17. J Biol Chem, 285(26), 20358-68, 2010

Limpert, AS, Carter, BD. Axonal neuregulin 1 type III activates NF-kappaB in Schwann cells during myelin formation. J Biol Chem, 285(22), 16614-22, 2010

Scheib, JL, Carter, BD. Eaters of the dead: Glial precursors clear neuron corpses during development. Cell Cycle, 9(10), 2010

Antar, AA, Konopka, JL, Campbell, JA, Henry, RA, Perdigoto, AL, Carter, BD, Pozzi, A, Abel, TW, Dermody, TS. Junctional adhesion molecule-A is required for hematogenous dissemination of reovirus. Cell Host Microbe, 5(1), 59-71, 2009 PMCID:2642927

Vilar, M, Charalampopoulos, I, Kenchappa, RS, Reversi, A, Klos-Applequist, JM, Karaca, E, Simi, A, Spuch, C, Choi, S, Friedman, WJ, Ericson, J, Schiavo, G, Carter, BD, Ib?!??ez, CF. Ligand-independent signaling by disulfide-crosslinked dimers of the p75 neurotrophin receptor. J Cell Sci, 122(Pt 18), 3351-7, 2009 PMCID:2736866

Vilar, M, Charalampopoulos, I, Kenchappa, RS, Simi, A, Karaca, E, Reversi, A, Choi, S, Bothwell, M, Mingarro, I, Friedman, WJ, Schiavo, G, Bastiaens, PI, Verveer, PJ, Carter, BD, Ib?!??ez, CF. Activation of the p75 neurotrophin receptor through conformational rearrangement of disulphide-linked receptor dimers. Neuron, 62(1), 72-83, 2009

Wu, HH, Bellmunt, E, Scheib, JL, Venegas, V, Burkert, C, Reichardt, LF, Zhou, Z, Fari??as, I, Carter, BD. Glial precursors clear sensory neuron corpses during development via Jedi-1, an engulfment receptor. Nat Neurosci, 12(12), 1534-41, 2009

Bertrand, MJ, Kenchappa, RS, Andrieu, D, Leclercq-Smekens, M, Nguyen, HN, Carter, BD, Muscatelli, F, Barker, PA, De Backer, O. NRAGE, a p75NTR adaptor protein, is required for developmental apoptosis in vivo. Cell Death Differ, 2008 PMCID:2735073

Hundahl, CA, Allen, GC, Nyengaard, JR, Dewilde, S, Carter, BD, Kelsen, J, Hay-Schmidt, A. Neuroglobin in the Rat Brain: Localization. Neuroendocrinology, 2008

Korade, Z, Kenchappa, RS, Mirnics, K, Carter, BD. NRIF is a Regulator of Neuronal Cholesterol Biosynthesis Genes. J Mol Neurosci, 2008

Schlisio, S, Kenchappa, RS, Vredeveld, LC, George, RE, Stewart, R, Greulich, H, Shahriari, K, Nguyen, NV, Pigny, P, Dahia, PL, Pomeroy, SL, Maris, JM, Look, AT, Meyerson, M, Peeper, DS, Carter, BD, Kaelin, WG. The kinesin KIF1B{beta} acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor. Genes Dev, 22(7), 884-93, 2008 PMCID:2279200

Volosin, M, Trotter, C, Cragnolini, A, Kenchappa, RS, Light, M, Hempstead, BL, Carter, BD, Friedman, WJ. Induction of proneurotrophins and activation of p75NTR-mediated apoptosis via neurotrophin receptor-interacting factor in hippocampal neurons after seizures. J Neurosci, 28(39), 9870-9, 2008 PMCID:2578816

Yoon, C, Korade, Z, Carter, BD. Protein Kinase A-Induced Phosphorylation of the p65 Subunit of Nuclear Factor-{kappa}B Promotes Schwann Cell Differentiation into a Myelinating Phenotype. J Neurosci, 28(14), 3738-46, 2008

Carter, BD. A Bex-cycle built for two. EMBO Rep, 7(4), 382-4, 2006 PMCID:1456923

Kenchappa, RS, Zampieri, N, Chao, MV, Barker, PA, Teng, HK, Hempstead, BL, Carter, BD. Ligand-dependent cleavage of the P75 neurotrophin receptor is necessary for NRIF nuclear translocation and apoptosis in sympathetic neurons. Neuron, 50(2), 219-32, 2006

Qu, S, Rinehart, C, Wu, HH, Wang, SE, Carter, B, Xin, H, Kotlikoff, M, Arteaga, CL. Gene targeting of ErbB3 using a Cre-mediated unidirectional DNA inversion strategy. Genesis, 44(10), 477-86, 2006

Geetha, T, Kenchappa, RS, Wooten, MW, Carter, BD. TRAF6-mediated ubiquitination regulates nuclear translocation of NRIF, the p75 receptor interactor. EMBO J, 24(22), 3859-68, 2005 PMCID:1283944

Lee, S, Nakamura, E, Yang, H, Wei, W, Linggi, MS, Sajan, MP, Farese, RV, Freeman, RS, Carter, BD, Kaelin, WG, Schlisio, S. Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: Developmental culling and cancer. Cancer Cell, 8(2), 155-167, 2005

Linggi, Michelle S, Burke, Tara L, Williams, B Blairanne, Harrington, Anthony, Kraemer, Rosemary, Hempstead, Barbara L, Yoon, Sung Ok, Carter, Bruce D. NRIF is an essential mediator of apoptotic signaling by the p75 neurotrophin receptor. J Biol Chem, 2005

Gentry, Jannifer J, Barker, Philip A, Carter, Bruce D. The p75 neurotrophin receptor: multiple interactors and numerous functions. Prog Brain Res, 146, 25-39, 2004

Gentry, Jennifer J., Rutkoski, Nancy J., Burke, Tara L., Carter, Bruce D.. A functional interaction between the p75 neurotrophin receptor interacting factors, TRAF6 and NRIF. J Biol Chem, 2004

Yeiser, E Carden, Rutkoski, Nancy J, Naito, Asuka, Inoue, Jun-ichiro, Carter, Bruce D. Neurotrophin signaling through the p75 receptor is deficient in traf6-/- mice. J Neurosci, 24(46), 10521-9, 2004

Nickols, Joshua C, Valentine, William, Kanwal, Sujata, Carter, Bruce D. Activation of the transcription factor NF-kappaB in Schwann cells is required for peripheral myelin formation. Nat Neurosci, 6(2), 161-7, 2003

Fainzilber, Mike, Carter, Bruce D. From neurotrophins to immunotrophins. NGF 2002: The 7th international conference on NGF and related molecules. EMBO Rep, 3(11), 1029-34, 2002 PMCID:1307597

Palmada, M, Kanwal, S, Rutkoski, N J, Gustafson-Brown, C, Johnson, R S, Wisdom, R, Carter, B D. c-jun is essential for sympathetic neuronal death induced by NGF withdrawal but not by p75 activation. J Cell Biol, 158(3), 453-61, 2002 PMCID:2173823

Dobrowsky, R T, Carter, B D. p75 neurotrophin receptor signaling: mechanisms for neurotrophic modulation of cell stress. J Neurosci Res, 61(3), 237-43, 2000

Gentry, J J, Casaccia-Bonnefil, P, Carter, B D. Nerve growth factor activation of nuclear factor kappaB through its p75 receptor is an anti-apoptotic signal in RN22 schwannoma cells. J Biol Chem, 275(11), 7558-65, 2000

Casademunt, E, Carter, B D, Benzel, I, Frade, J M, Dechant, G, Barde, Y A. The zinc finger protein NRIF interacts with the neurotrophin receptor p75(NTR) and participates in programmed cell death. EMBO J, 18(21), 6050-61, 1999 PMCID:1171670

Chao, M., Casaccia-Bonnefil, P., Carter, B., Chittka, A., Kong, H. and Yoon, S.O. Neurotrophin receptors: mediators of life and death. Brain Res. Brain Res. Rev., 26, 295-301, 1998

Dobrowsky, R T, Carter, B D. Coupling of the p75 neurotrophin receptor to sphingolipid signaling. Ann N Y Acad Sci, 845, 32-45, 1998

Yoon SO, Casaccia-Bonnefil P, Carter BD and Chao MV. Competitive signaling between TrkA and p75 NGF receptors determines cell survival. J Neurosci, 18, 3273-3281, 1998

Carter, B D, Lewin, G R. Neurotrophins live or let die: does p75NTR decide. Neuron, 18(2), 187-90, 1997

Carter, B D, Dechant, G, Frade, J M, Kaltschmidt, C, Barde, Y A. Neurotrophins and their p75 receptor. Cold Spring Harb Symp Quant Biol, 61, 407-15, 1996

Carter, B D, Kaltschmidt, C, Kaltschmidt, B, Offenh??user, N, B??hm-Matthaei, R, Baeuerle, P A, Barde, Y A. Selective activation of NF-kappa B by nerve growth factor through the neurotrophin receptor p75. Science, 272(5261), 542-5, 1996

Casaccia-Bonnefil, P, Carter, B D, Dobrowsky, R T, Chao, M V. Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75. Nature, 383(6602), 716-9, 1996

Strohmaier, C, Carter, B D, Urfer, R, Barde, Y A, Dechant, G. A splice variant of the neurotrophin receptor trkB with increased specificity for brain-derived neurotrophic factor. EMBO J, 15(13), 3332-7, 1996 PMCID:451896

Zirrgiebel, U., Ohga, Y., Carter, B., Berninger, B., Inagaki, N., Thoenen, H. and D. Lindholm. Characterization of Trk B receptor-mediated signaling pathways in rat cerebellar granule neurons; their importance for neuronal survival. J. Neurochem., 65:2241-2250, 1995.

Biffo, S, Offenh??user, N, Carter, B D, Barde, Y A. Selective binding and internalisation by truncated receptors restrict the availability of BDNF during development. Development, 121(8), 2461-70, 1995

Carter, B D, Zirrgiebel, U, Barde, Y A. Differential regulation of p21ras activation in neurons by nerve growth factor and brain-derived neurotrophic factor. J Biol Chem, 270(37), 21751-7, 1995

Carter, B D, Medzihradsky, F. Go mediates the coupling of the mu opioid receptor to adenylyl cyclase in cloned neural cells and brain. Proc Natl Acad Sci U S A, 90(9), 4062-6, 1993 PMCID:46446

Carter, B D, Medzihradsky, F. Receptor mechanisms of opioid tolerance in SH-SY5Y human neural cells. Mol Pharmacol, 43(3), 465-73, 1993

Carter, B D, Medzihradsky, F. Opioid signal transduction in intact and fragmented SH-SY5Y neural cells. J Neurochem, 58(5), 1611-9, 1992

Medzihradsky, F. and B.D. Carter. Opioid receptor mechanisms. Chapt. 10 of Biochemistry and Physiology of Substance Abuse (Watson, R.R. ed.) CRC Press Inc., Boca Raton, Fl., 1991

Clark, M J, Carter, B D, Medzihradsky, F. Selectivity of ligand binding to opioid receptors in brain membranes from the rat, monkey and guinea pig. Eur J Pharmacol, 148(3), 343-51, 1988


Postdoctoral Position Available
Yes

Postdoctoral Position Details
Please apply by e-mail to
bruce.carter@vanderbilt.edu
sending CV and names
of three references.

Updated Date
03/13/2012