title: Hrk/DP5 contributes to the apoptosis of select neuronal populations but is dispensable for haematopoietic cell apoptosis.
abstract: The pro-apoptotic BH3-only members of the Bcl2 family, crucial initiators of cell death, are activated by a diverse array of developmental cues or experimentally applied stress stimuli. We have investigated, through gene targeting in mice, the biological roles for the BH3-only family member HRK (also known as DP5) in apoptosis regulation. Hrk gene expression was found to be restricted to cells and tissues of the central and peripheral nervous systems. Sensory neurons from mice lacking Hrk were less sensitive to apoptosis induced by nerve growth factor (NGF) withdrawal, consistent with the induction of Hrk following NGF deprivation. By contrast, cerebellar granule neurons that upregulate Hrk upon transfer to low-K+ medium underwent apoptosis normally under these conditions in the absence of Hrk. Furthermore, loss of Hrk was not sufficient to rescue the neuronal degeneration in lurcher mutant mice. Despite previous reports, no evidence was found for Hrk expression or induction in growth-factor-dependent haematopoietic cell lines following withdrawal of their requisite cytokine, and haematopoietic progenitors lacking HRK died normally in response to cytokine deprivation. These results demonstrate that HRK contributes to apoptosis signalling elicited by trophic factor withdrawal in certain neuronal populations but is dispensable for apoptosis of haematopoietic cells.
authors.affiliation: The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
authors.forename: Leigh
authors.initials: L
authors.lastname: Coultas
authors.forename: Susanna
authors.initials: S
authors.lastname: Terzano
authors.forename: Tim
authors.initials: T
authors.lastname: Thomas
authors.forename: Anne
authors.initials: A
authors.lastname: Voss
authors.forename: Kate
authors.initials: K
authors.lastname: Reid
authors.forename: Edouard G
authors.initials: EG
authors.lastname: Stanley
authors.forename: Clare L
authors.initials: CL
authors.lastname: Scott
authors.forename: Philippe
authors.initials: P
authors.lastname: Bouillet
authors.forename: Perry
authors.initials: P
authors.lastname: Bartlett
authors.forename: Jonathan
authors.initials: J
authors.lastname: Ham
authors.forename: Jerry M
authors.initials: JM
authors.lastname: Adams
authors.forename: Andreas
authors.initials: A
authors.lastname: Strasser
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002531:Cerebellum / Q000166:cytology; D016207:Cytokines / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology; D018390:Gene Targeting; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008818:Mice, Neurologic Mutants; D020932:Nerve Growth Factor / Q000378:metabolism; D009420:Nervous System / Q000033:anatomy & histology / Q000196:embryology / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D016207:Cytokines; C107631:Hrk protein, mouse; D009479:Neuropeptides; D020932:Nerve Growth Factor