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p75 neurotrophin receptor as a modulator of survival and death decisions
Author(s) -
CasacciaBonnefil Patrizia,
Gu Chenghua,
Khursigara Gus,
Chao Moses V.
Publication year - 1999
Publication title -
microscopy research and technique
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 118
eISSN - 1097-0029
pISSN - 1059-910X
DOI - 10.1002/(sici)1097-0029(19990515/01)45:4/5<217::aid-jemt5>3.0.co;2-5
Subject(s) - trk receptor , neurotrophin , low affinity nerve growth factor receptor , tropomyosin receptor kinase c , receptor tyrosine kinase , biology , microbiology and biotechnology , receptor , programmed cell death , tropomyosin receptor kinase a , ror1 , neurotrophic factors , tropomyosin receptor kinase b , signal transduction , neuroscience , platelet derived growth factor receptor , growth factor , apoptosis , genetics
The p75 receptor is the founding member of the TNF receptor superfamily. Members in this receptor family share a common cysteine motif repeated two to six times that serves as the ligand binding domain. In addition, several members contain a cytoplasmic region designated the death domain. The neurotrophins NGF, BDNF, NT‐3, and NT‐4 each bind to the p75 receptor and also more selectively to members of the Trk family of receptor tyrosine kinases. Although the biological functions of p75 have been elusive, recent experimental evidence supports an involvement of this receptor in apoptosis. This presents a counter‐intuitive function for neurotrophins, which are normally required for the survival of neurons during development. The life‐and‐death decisions by neurotrophins appear to be governed by the level of expression and signaling activities of the p75 and Trk tyrosine kinase receptors and their downstream effector molecules. The generation of the correct number of cells in the nervous system is a highly controlled and coordinated process that is the consequence of cell proliferation and cell death decisions. The appropriate number of neuronal and glial cells formed during development guarantees the establishment of proper innervation and functional synaptic connections. One common mechanism to account for the number of viable cells is the ability to form ligand‐receptor complexes that promote cell survival under conditions of limiting concentrations of trophic factors. Another diametrically opposed mechanism is to produce ligand‐receptor interactions that can activate programmed cell death directly. Microsc. Res. Tech. 45:217–224, 1999. © 1999 Wiley‐Liss, Inc.