Bruce Carter
Faculty Member
Last active: 4/4/2019


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.


The following timeline graph is generated from all co-authored publications.

Featured publications are shown below:

  1. Retrograde Degenerative Signaling Mediated by the p75 Neurotrophin Receptor Requires p150 Deacetylation by Axonal HDAC1. Pathak A, Stanley EM, Hickman FE, Wallace N, Brewer B, Li D, Gluska S, Perlson E, Fuhrmann S, Akassoglou K, Bronfman F, Casaccia P, Burnette DT, Carter BD (2018) Dev Cell 46(3): 376-387.e7
    › Primary publication · 30086304 (PubMed) · PMC6093198 (PubMed Central)
  2. Neurotrophin Responsiveness of Sympathetic Neurons Is Regulated by Rapid Mobilization of the p75 Receptor to the Cell Surface through TrkA Activation of Arf6. Hickman FE, Stanley EM, Carter BD (2018) J Neurosci 38(24): 5606-5619
    › Primary publication · 29789375 (PubMed) · PMC6001035 (PubMed Central)
  3. Myelin-Associated Glycoprotein Inhibits Schwann Cell Migration and Induces Their Death. Chaudhry N, Bachelin C, Zujovic V, Hilaire M, Baldwin KT, Follis RM, Giger R, Carter BD, Baron-Van Evercooren A, Filbin MT (2017) J Neurosci 37(24): 5885-5899
    › Primary publication · 28522736 (PubMed) · PMC5473206 (PubMed Central)
  4. A Chimeric Egfr Protein Reporter Mouse Reveals Egfr Localization and Trafficking In Vivo. Yang YP, Ma H, Starchenko A, Huh WJ, Li W, Hickman FE, Zhang Q, Franklin JL, Mortlock DP, Fuhrmann S, Carter BD, Ihrie RA, Coffey RJ (2017) Cell Rep 19(6): 1257-1267
    › Primary publication · 28494873 (PubMed) · PMC5517093 (PubMed Central)
  5. Apoptosis and Vocal Fold Disease: Clinically Relevant Implications of Epithelial Cell Death. Novaleski CK, Carter BD, Sivasankar MP, Ridner SH, Dietrich MS, Rousseau B (2017) J Speech Lang Hear Res 60(5): 1264-1272
    › Primary publication · 28492834 (PubMed) · PMC5755547 (PubMed Central)
  6. Expression of MYCN in Multipotent Sympathoadrenal Progenitors Induces Proliferation and Neural Differentiation, but Is Not Sufficient for Tumorigenesis. Mobley BC, Kwon M, Kraemer BR, Hickman FE, Qiao J, Chung DH, Carter BD (2015) PLoS One 10(7): e0133897
    › Primary publication · 26222553 (PubMed) · PMC4519318 (PubMed Central)
  7. Conformational Stability and Pathogenic Misfolding of the Integral Membrane Protein PMP22. Schlebach JP, Narayan M, Alford C, Mittendorf KF, Carter BD, Li J, Sanders CR (2015) J Am Chem Soc 137(27): 8758-68
    › Primary publication · 26102530 (PubMed) · PMC4507940 (PubMed Central)
  8. Integrin α3β1 regulates kidney collecting duct development via TRAF6-dependent K63-linked polyubiquitination of Akt. Yazlovitskaya EM, Tseng HY, Viquez O, Tu T, Mernaugh G, McKee KK, Riggins K, Quaranta V, Pathak A, Carter BD, Yurchenco P, Sonnenberg A, Böttcher RT, Pozzi A, Zent R (2015) Mol Biol Cell 26(10): 1857-74
    › Primary publication · 25808491 (PubMed) · PMC4436831 (PubMed Central)
  9. Neurotrophic factors. Preface. Lewin GR, Carter BD (2014) Handb Exp Pharmacol : v-vi
    › Primary publication · 24941498 (PubMed)
  10. A role for the p75 neurotrophin receptor in axonal degeneration and apoptosis induced by oxidative stress. Kraemer BR, Snow JP, Vollbrecht P, Pathak A, Valentine WM, Deutch AY, Carter BD (2014) J Biol Chem 289(31): 21205-16
    › Primary publication · 24939843 (PubMed) · PMC4118083 (PubMed Central)
  11. The adaptor protein GULP promotes Jedi-1-mediated phagocytosis through a clathrin-dependent mechanism. Sullivan CS, Scheib JL, Ma Z, Dang RP, Schafer JM, Hickman FE, Brodsky FM, Ravichandran KS, Carter BD (2014) Mol Biol Cell 25(12): 1925-36
    › Primary publication · 24743597 (PubMed) · PMC4055271 (PubMed Central)
  12. The biological functions and signaling mechanisms of the p75 neurotrophin receptor. Kraemer BR, Yoon SO, Carter BD (2014) Handb Exp Pharmacol : 121-64
    › Primary publication · 24668472 (PubMed)
  13. The p75 neurotrophin receptor evades the endolysosomal route in neuronal cells, favouring multivesicular bodies specialised for exosomal release. Escudero CA, Lazo OM, Galleguillos C, Parraguez JI, Lopez-Verrilli MA, Cabeza C, Leon L, Saeed U, Retamal C, Gonzalez A, Marzolo MP, Carter BD, Court FA, Bronfman FC (2014) J Cell Sci 127(Pt 9): 1966-79
    › Primary publication · 24569882 (PubMed) · PMC4004974 (PubMed Central)
  14. p75 neurotrophin receptor cleavage by α- and γ-secretases is required for neurotrophin-mediated proliferation of brain tumor-initiating cells. Forsyth PA, Krishna N, Lawn S, Valadez JG, Qu X, Fenstermacher DA, Fournier M, Potthast L, Chinnaiyan P, Gibney GT, Zeinieh M, Barker PA, Carter BD, Cooper MK, Kenchappa RS (2014) J Biol Chem 289(12): 8067-85
    › Primary publication · 24519935 (PubMed) · PMC3961639 (PubMed Central)
  15. Abnormal junctions and permeability of myelin in PMP22-deficient nerves. Guo J, Wang L, Zhang Y, Wu J, Arpag S, Hu B, Imhof BA, Tian X, Carter BD, Suter U, Li J (2014) Ann Neurol 75(2): 255-65
    › Primary publication · 24339129 (PubMed) · PMC4206215 (PubMed Central)
  16. Reversible folding of human peripheral myelin protein 22, a tetraspan membrane protein. Schlebach JP, Peng D, Kroncke BM, Mittendorf KF, Narayan M, Carter BD, Sanders CR (2013) Biochemistry 52(19): 3229-41
    › Primary publication · 23639031 (PubMed) · PMC3762913 (PubMed Central)
  17. miR-153 regulates SNAP-25, synaptic transmission, and neuronal development. Wei C, Thatcher EJ, Olena AF, Cha DJ, Perdigoto AL, Marshall AF, Carter BD, Broadie K, Patton JG (2013) PLoS One 8(2): e57080
    › Primary publication · 23451149 (PubMed) · PMC3581580 (PubMed Central)
  18. NF-κB forms a complex with the chromatin remodeler BRG1 to regulate Schwann cell differentiation. Limpert AS, Bai S, Narayan M, Wu J, Yoon SO, Carter BD, Lu QR (2013) J Neurosci 33(6): 2388-97
    › Primary publication · 23392668 (PubMed) · PMC3711599 (PubMed Central)
  19. Jedi-1 and MEGF10 signal engulfment of apoptotic neurons through the tyrosine kinase Syk. Scheib JL, Sullivan CS, Carter BD (2012) J Neurosci 32(38): 13022-31
    › Primary publication · 22993420 (PubMed) · PMC3464495 (PubMed Central)
  20. Expression and localization of myosin-1d in the developing nervous system. Benesh AE, Fleming JT, Chiang C, Carter BD, Tyska MJ (2012) Brain Res : 9-22
    › Primary publication · 22284616 (PubMed) · PMC3278530 (PubMed Central)
  21. 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. Tep C, Kim ML, Opincariu LI, Limpert AS, Chan JR, Appel B, Carter BD, Yoon SO (2012) J Biol Chem 287(2): 1600-8
    › Primary publication · 22128191 (PubMed) · PMC3256919 (PubMed Central)
  22. (R)-Profens are substrate-selective inhibitors of endocannabinoid oxygenation by COX-2. Duggan KC, Hermanson DJ, Musee J, Prusakiewicz JJ, Scheib JL, Carter BD, Banerjee S, Oates JA, Marnett LJ (2011) Nat Chem Biol 7(11): 803-9
    › Primary publication · 22053353 (PubMed) · PMC3298755 (PubMed Central)
  23. Mutation analysis of HIF prolyl hydroxylases (PHD/EGLN) in individuals with features of phaeochromocytoma and renal cell carcinoma susceptibility. 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 (2011) Endocr Relat Cancer 18(1): 73-83
    › Primary publication · 20959442 (PubMed) · PMC3006001 (PubMed Central)
  24. A novel role for PTEN in the inhibition of neurite outgrowth by myelin-associated glycoprotein in cortical neurons. Perdigoto AL, Chaudhry N, Barnes GN, Filbin MT, Carter BD (2011) Mol Cell Neurosci 46(1): 235-44
    › Primary publication · 20869442 (PubMed) · PMC3018674 (PubMed Central)
  25. Eaters of the dead: glial precursors clear neuron corpses during development. Scheib JL, Carter BD (2010) Cell Cycle 9(10): 1867-8
    › Primary publication · 20436291 (PubMed) · PMC3093807 (PubMed Central)
  26. Degeneration keeps axons on the straight and narrow. Carter BD (2010) Nat Neurosci 13(5): 526-8
    › Primary publication · 20421896 (PubMed)
  27. 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. Kenchappa RS, Tep C, Korade Z, Urra S, Bronfman FC, Yoon SO, Carter BD (2010) J Biol Chem 285(26): 20358-68
    › Primary publication · 20421303 (PubMed) · PMC2888447 (PubMed Central)
  28. Axonal neuregulin 1 type III activates NF-kappaB in Schwann cells during myelin formation. Limpert AS, Carter BD (2010) J Biol Chem 285(22): 16614-22
    › Primary publication · 20360002 (PubMed) · PMC2878070 (PubMed Central)
  29. The p75 neurotrophin receptor, semaphorins, and sympathetic traffic in the heart. Carter BD, Feng N, Paolocci N (2010) Am J Physiol Heart Circ Physiol 298(6): H1633-6
    › Primary publication · 20304820 (PubMed) · PMC2886656 (PubMed Central)
  30. Glial precursors clear sensory neuron corpses during development via Jedi-1, an engulfment receptor. Wu HH, Bellmunt E, Scheib JL, Venegas V, Burkert C, Reichardt LF, Zhou Z, Fariñas I, Carter BD (2009) Nat Neurosci 12(12): 1534-41
    › Primary publication · 19915564 (PubMed) · PMC2834222 (PubMed Central)
  31. Ligand-independent signaling by disulfide-crosslinked dimers of the p75 neurotrophin receptor. 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, Ibáñez CF (2009) J Cell Sci 122(Pt 18): 3351-7
    › Primary publication · 19706676 (PubMed) · PMC2736866 (PubMed Central)
  32. Activation of the p75 neurotrophin receptor through conformational rearrangement of disulphide-linked receptor dimers. 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, Ibáñez CF (2009) Neuron 62(1): 72-83
    › Primary publication · 19376068 (PubMed) · PMC2810632 (PubMed Central)
  33. Junctional adhesion molecule-A is required for hematogenous dissemination of reovirus. Antar AA, Konopka JL, Campbell JA, Henry RA, Perdigoto AL, Carter BD, Pozzi A, Abel TW, Dermody TS (2009) Cell Host Microbe 5(1): 59-71
    › Primary publication · 19154988 (PubMed) · PMC2642927 (PubMed Central)
  34. Induction of proneurotrophins and activation of p75NTR-mediated apoptosis via neurotrophin receptor-interacting factor in hippocampal neurons after seizures. Volosin M, Trotter C, Cragnolini A, Kenchappa RS, Light M, Hempstead BL, Carter BD, Friedman WJ (2008) J Neurosci 28(39): 9870-9
    › Primary publication · 18815271 (PubMed) · PMC2578816 (PubMed Central)
  35. NRAGE, a p75NTR adaptor protein, is required for developmental apoptosis in vivo. Bertrand MJ, Kenchappa RS, Andrieu D, Leclercq-Smekens M, Nguyen HN, Carter BD, Muscatelli F, Barker PA, De Backer O (2008) Cell Death Differ 15(12): 1921-9
    › Primary publication · 18772898 (PubMed) · PMC2735073 (PubMed Central)
  36. NRIF is a regulator of neuronal cholesterol biosynthesis genes. Korade Z, Kenchappa RS, Mirnics K, Carter BD (2009) J Mol Neurosci 38(2): 152-8
    › Primary publication · 18677445 (PubMed) · PMC3118441 (PubMed Central)
  37. Neuroglobin in the rat brain: localization. Hundahl CA, Allen GC, Nyengaard JR, Dewilde S, Carter BD, Kelsen J, Hay-Schmidt A (2008) Neuroendocrinology 88(3): 173-82
    › Primary publication · 18451642 (PubMed)
  38. Protein kinase A-induced phosphorylation of the p65 subunit of nuclear factor-kappaB promotes Schwann cell differentiation into a myelinating phenotype. Yoon C, Korade Z, Carter BD (2008) J Neurosci 28(14): 3738-46
    › Primary publication · 18385332 (PubMed) · PMC6671072 (PubMed Central)
  39. The kinesin KIF1Bbeta acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor. 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 (2008) Genes Dev 22(7): 884-93
    › Primary publication · 18334619 (PubMed) · PMC2279200 (PubMed Central)
  40. Ligand-dependent cleavage of the P75 neurotrophin receptor is necessary for NRIF nuclear translocation and apoptosis in sympathetic neurons. Kenchappa RS, Zampieri N, Chao MV, Barker PA, Teng HK, Hempstead BL, Carter BD (2006) Neuron 50(2): 219-32
    › Primary publication · 16630834 (PubMed)
  41. A Bex-cycle built for two. Carter BD (2006) EMBO Rep 7(4): 382-4
    › Primary publication · 16585938 (PubMed) · PMC1456923 (PubMed Central)
  42. TRAF6-mediated ubiquitination regulates nuclear translocation of NRIF, the p75 receptor interactor. Geetha T, Kenchappa RS, Wooten MW, Carter BD (2005) EMBO J 24(22): 3859-68
    › Primary publication · 16252010 (PubMed) · PMC1283944 (PubMed Central)
  43. Neuronal apoptosis linked to EglN3 prolyl hydroxylase and familial pheochromocytoma genes: developmental culling and cancer. Lee S, Nakamura E, Yang H, Wei W, Linggi MS, Sajan MP, Farese RV, Freeman RS, Carter BD, Kaelin WG, Schlisio S (2005) Cancer Cell 8(2): 155-67
    › Primary publication · 16098468 (PubMed)
  44. Neurotrophin receptor interacting factor (NRIF) is an essential mediator of apoptotic signaling by the p75 neurotrophin receptor. Linggi MS, Burke TL, Williams BB, Harrington A, Kraemer R, Hempstead BL, Yoon SO, Carter BD (2005) J Biol Chem 280(14): 13801-8
    › Primary publication · 15668238 (PubMed)
  45. Neurotrophin signaling through the p75 receptor is deficient in traf6-/- mice. Yeiser EC, Rutkoski NJ, Naito A, Inoue J, Carter BD (2004) J Neurosci 24(46): 10521-9
    › Primary publication · 15548667 (PubMed) · PMC6730299 (PubMed Central)
  46. A functional interaction between the p75 neurotrophin receptor interacting factors, TRAF6 and NRIF. Gentry JJ, Rutkoski NJ, Burke TL, Carter BD (2004) J Biol Chem 279(16): 16646-56
    › Primary publication · 14960584 (PubMed)
  47. The p75 neurotrophin receptor: multiple interactors and numerous functions. Gentry JJ, Barker PA, Carter BD (2004) Prog Brain Res : 25-39
    › Primary publication · 14699954 (PubMed)
  48. Activation of the transcription factor NF-kappaB in Schwann cells is required for peripheral myelin formation. Nickols JC, Valentine W, Kanwal S, Carter BD (2003) Nat Neurosci 6(2): 161-7
    › Primary publication · 12514737 (PubMed)
  49. From neurotrophins to immunotrophins. NGF 2002: The 7th international conference on NGF and related molecules. Fainzilber M, Carter BD (2002) EMBO Rep 3(11): 1029-34
    › Primary publication · 12429612 (PubMed) · PMC1307597 (PubMed Central)
  50. c-jun is essential for sympathetic neuronal death induced by NGF withdrawal but not by p75 activation. Palmada M, Kanwal S, Rutkoski NJ, Gustafson-Brown C, Johnson RS, Wisdom R, Carter BD, Gufstafson-Brown C (2002) J Cell Biol 158(3): 453-61
    › Primary publication · 12163468 (PubMed) · PMC2173823 (PubMed Central)
  51. p75 neurotrophin receptor signaling: mechanisms for neurotrophic modulation of cell stress? Dobrowsky RT, Carter BD (2000) J Neurosci Res 61(3): 237-43
    › Primary publication · 10900070 (PubMed)
  52. Nerve growth factor activation of nuclear factor kappaB through its p75 receptor is an anti-apoptotic signal in RN22 schwannoma cells. Gentry JJ, Casaccia-Bonnefil P, Carter BD (2000) J Biol Chem 275(11): 7558-65
    › Primary publication · 10713062 (PubMed)
  53. The zinc finger protein NRIF interacts with the neurotrophin receptor p75(NTR) and participates in programmed cell death. Casademunt E, Carter BD, Benzel I, Frade JM, Dechant G, Barde YA (1999) EMBO J 18(21): 6050-61
    › Primary publication · 10545116 (PubMed) · PMC1171670 (PubMed Central)
  54. Coupling of the p75 neurotrophin receptor to sphingolipid signaling. Dobrowsky RT, Carter BD (1998) Ann N Y Acad Sci : 32-45
    › Primary publication · 9668341 (PubMed)
  55. Neurotrophins and their p75 receptor. Carter BD, Dechant G, Frade JM, Kaltschmidt C, Barde YA (1996) Cold Spring Harb Symp Quant Biol : 407-15
    › Primary publication · 9246469 (PubMed)
  56. Neurotrophins live or let die: does p75NTR decide? Carter BD, Lewin GR (1997) Neuron 18(2): 187-90
    › Primary publication · 9052790 (PubMed)
  57. Death of oligodendrocytes mediated by the interaction of nerve growth factor with its receptor p75. Casaccia-Bonnefil P, Carter BD, Dobrowsky RT, Chao MV (1996) Nature 383(6602): 716-9
    › Primary publication · 8878481 (PubMed)
  58. A splice variant of the neurotrophin receptor trkB with increased specificity for brain-derived neurotrophic factor. Strohmaier C, Carter BD, Urfer R, Barde YA, Dechant G (1996) EMBO J 15(13): 3332-7
    › Primary publication · 8670834 (PubMed) · PMC451896 (PubMed Central)
  59. Selective activation of NF-kappa B by nerve growth factor through the neurotrophin receptor p75. Carter BD, Kaltschmidt C, Kaltschmidt B, Offenhäuser N, Böhm-Matthaei R, Baeuerle PA, Barde YA (1996) Science 272(5261): 542-5
    › Primary publication · 8614802 (PubMed)
  60. Receptor mechanisms of opioid tolerance in SH-SY5Y human neural cells. Carter BD, Medzihradsky F (1993) Mol Pharmacol 43(3): 465-73
    › Primary publication · 8383804 (PubMed)
  61. Go mediates the coupling of the mu opioid receptor to adenylyl cyclase in cloned neural cells and brain. Carter BD, Medzihradsky F (1993) Proc Natl Acad Sci U S A 90(9): 4062-6
    › Primary publication · 8097884 (PubMed) · PMC46446 (PubMed Central)
  62. Selective binding and internalisation by truncated receptors restrict the availability of BDNF during development. Biffo S, Offenhäuser N, Carter BD, Barde YA (1995) Development 121(8): 2461-70
    › Primary publication · 7671810 (PubMed)
  63. Differential regulation of p21ras activation in neurons by nerve growth factor and brain-derived neurotrophic factor. Carter BD, Zirrgiebel U, Barde YA (1995) J Biol Chem 270(37): 21751-7
    › Primary publication · 7665594 (PubMed)
  64. Selectivity of ligand binding to opioid receptors in brain membranes from the rat, monkey and guinea pig. Clark MJ, Carter BD, Medzihradsky F (1988) Eur J Pharmacol 148(3): 343-51
    › Primary publication · 2898375 (PubMed)
  65. Opioid signal transduction in intact and fragmented SH-SY5Y neural cells. Carter BD, Medzihradsky F (1992) J Neurochem 58(5): 1611-9
    › Primary publication · 1560222 (PubMed)