The catalytic subunit of telomerase is expressed in developing brain neurons and serves a cell survival-promoting function.
Telomerase, a specialized reverse transcriptase (RT) linked to cell immortalization and cancer, has been thought not to be expressed in postmitotic cells. We now report that telomerase activity and its essential catalytic subunit, telomerase reverse transcriptase (TERT), are expressed in neurons in the brains of rodents during embryonic and early postnatal development, and are subsequently downregulated. Suppression of TERT expression in cultured embryonic hippocampal neurons increases their vulnerability to apoptosis and excitotoxicity. Overexpression of TERT in PC12 cells suppresses apoptosis induced by trophic factor withdrawal. TERT exerts its anti-apoptotic action at an early stage of the cell death process prior to mitochondrial dysfunction and caspase activation. TERT may serve a neuron survival-promoting function in the developing brain, and downregulation of TERT in the adult brain may contribute to increased neuronal vulnerability in various age-related neurodegenerative disorders.
Fu
W
W
Sanders Brown Research Center on Aging, University of Kentucky, Lexington 40536, USA.
Killen
M
M
Culmsee
C
C
Dhar
S
S
Pandita
T K
TK
Mattson
M P
MP
D000375:Aging; D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000196:embryology / Q000201:enzymology* / Q000254:growth & development; D020169:Caspases / Q000378:metabolism; D020134:Catalytic Domain; D002470:Cell Survival; D002478:Cells, Cultured; D005314:Embryonic and Fetal Development; D018507:Gene Expression Regulation, Developmental; D015971:Gene Expression Regulation, Enzymologic; D046911:Macromolecular Substances; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000201:enzymology*; D012194:RNA-Directed DNA Polymerase / Q000235:genetics*; D051381:Rats; D019098:Telomerase / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*
D046911:Macromolecular Substances; D012194:RNA-Directed DNA Polymerase; D019098:Telomerase; D020169:Caspases