Presenilin-associated protein (PSAP) was originally identified as a mitochondrial proapoptotic protein. To further explore the apoptotic pathway that involves PSAP, our yeast two-hybrid screen revealed that PSAP interacts with a death receptor, DR6. DR6 is a relatively less common member of the death receptor family and has been shown to mediate the neurotoxicity of amyloid-β, mutant SOD1, and prion proteins and has also been implicated in the regulation of immune cell proliferation and differentiation. Our previous study showed that DR6 induces apoptosis via a unique mitochondria-dependent pathway different from the conventional death receptor-mediated extrinsic apoptotic pathways. Thus, the interaction of DR6 with PSAP established a direct molecular link between DR6 and mitochondrial apoptotic pathway. We investigated the possible role of PSAP in DR6-induced apoptosis. Interestingly, it was discovered that knockdown of PSAP strongly inhibited DR6-induced apoptosis. To further elucidate the mechanism by which PSAP mediates DR6-induced mitochondria-dependent apoptosis, our data demonstrated that knockdown of PSAP blocked DR6-induced Bax translocation and cytochrome c release from the mitochondria. Moreover, it was found that both PSAP and DR6 form complexes with Bax, but at different subcellular locations. The DR6-Bax complex was detected in the cytosolic fraction while the PSAP-Bax complex was detected in the mitochondrial fraction. The observation that knockdown of DR6 significantly reduced the amount of PSAP-Bax complex detected in mitochondria suggests a possibility that DR6-bound Bax is transferred to PSAP upon interaction with PSAP at the mitochondria, leading to cytochrome c release and eventually apoptosis.
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http://dx.doi.org/10.3233/JAD-191086 | DOI Listing |
iScience
December 2024
Division of Gene Regulation, Oncology Innovation Center, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
Cell cycle progression requires periodic gene expression through splicing control. However, the splicing factor that directly controls this cell cycle-dependent splicing remains unknown. Cell cycle-dependent expression of the (aurora kinase B) gene is essential for chromosome segregation and cytokinesis.
View Article and Find Full Text PDFMetachromatic leukodystrophy (MLD) is a genetic lysosomal disease. Here, we investigated the role of prosaposin () gene mutations in MLD. This current case report describes a female patient who presented with motor development regression at two years and five months of age.
View Article and Find Full Text PDFRev Med Inst Mex Seguro Soc
November 2024
Centro Médico ABC Campus, Servicio, Área o Departamento. Cuidad de México, México.
Adv Neurobiol
November 2024
Nathan Kline Institute for Psychiatric Research, Orangeburg, NY, USA.
Deficits in cognitive control contribute to behavioral impairments across neuropsychiatric disorders. Cognitive control is captured as a construct in the Research Domain Construct (RDoC) matrix and incorporate subdomains of goal selection, response selection, and performance monitoring. Relevant tasks for these subdomains include the "AX" version of the continuous performance task (goal selection) and the Go/NoGo and Stop-Signal reaction time tasks (response selection).
View Article and Find Full Text PDFArch Gerontol Geriatr
February 2025
Department of Pharmacy, Buddhachinaraj Hospital, Phitsanulok, Thailand.
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