The centrosome functions as the microtubule-organizing center (MTOC) and plays a vital role in organizing spindle poles during mitosis. The pair of centrioles, which are the core components of the centrosome, duplicate once per cell cycle, and this feature is essential for the establishment of spindle bipolarity. Here we describe the molecular characterization of a novel protein called CLERC (Centrosomal leucine-rich repeat and coiled-coil containing protein) which is a human ortholog of Chlamydomonas Vfl1 protein. CLERC is a protein of 1032 amino acids with a calculated molecular mass of 120 kDa and possesses leucine-rich repeat and coiled-coil domains. Database searches revealed that CLERC has homologs in a wide variety of eukaryotes and is evolutionarily conserved. Endogenous CLERC protein associated with the centrosomes throughout the cell cycle and accumulated during mitosis. RNAi-mediated depletion of CLERC blocked formation of normal mitotic spindles and led to multipolar spindles. Moreover, many of the spindle poles in CLERC depleted cells contained only one centriole, indicating that centrosomes split into fractions containing a single centriole. These data indicate that the major function of CLERC during mitosis is to maintain the structural integrity of centrosomes, thereby contributing to spindle bipolarity.
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http://dx.doi.org/10.4161/cc.7.17.6591 | DOI Listing |
Alzheimers Dement
December 2024
The Chinese University of Hong Kong, Hong Kong, Hong Kong, Hong Kong.
Background: Nucleotide-binding domain and leucine-rich repeat (LRR)-containing family protein 3 (NLRP3) is involved in neuroinflammation in Alzheimer's Disease (AD). Single nucleotide polymorphisms (SNPs) in the NLRP3 gene are associated with the risk of AD in different populations, however the relationship between NLRP3 SNPs and Hong Kong population has not been studied.
Method: In this study,12 intron SNPs and 2 exon SNPs were genotyped in 233 healthy controls and 323 mild cognitive impairments (MCI) patients from Hong Kong.
Alzheimers Dement
December 2024
University of Oxford, Oxford, United Kingdom.
Background: Alzheimer's (AD) and Parkinson's disease (PD) feature progressive neurodegeneration in a remarkably regionally selective manner. Post mortem studies have posited a role for cell autonomous mechanisms driving this, so we aimed to examine a live human induced pluripotent stem cell (iPSC) model to see whether it can replicate the phenomenon of selective neuronal vulnerability, so to better determine disease mechanisms and therapeutic targets.
Method: iPSC-derived neurons offer a rare opportunity to examine cell autonomous vulnerability in live human cells.
Cell Commun Signal
January 2025
Key Laboratory of Research on Clinical Molecular Diagnosis for High Incidence Diseases in Western Guangxi of Guangxi Higher Education Institutions, Reproductive Medicine of Guangxi Medical and Health Key Discipline Construction Project, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
Leucine-rich repeat kinase 2 (LRRK2) is a ROCO family member which its mutation is closely related with Parkinson's disease, and LRRK2 is widely involved into the regulation of autophagy, vesicle transport and neuronal proliferation. However, the roles of LRRK2 during mammalian oocyte maturation are still largely unclear. In present study, we disturbed the activity of LRRK2 and showed its essential roles in porcine oocytes.
View Article and Find Full Text PDFAutophagy
January 2025
Institute for Experimental Pediatric Hematology and Oncology, Goethe University Frankfurt, Frankfurt am Main, Germany.
Lysosomes are the major cellular organelles responsible for nutrient recycling and degradation of cellular material. Maintenance of lysosomal integrity is essential for cellular homeostasis and lysosomal membrane permeabilization (LMP) sensitizes toward cell death. Damaged lysosomes are repaired or degraded via lysophagy, during which glycans, exposed on ruptured lysosomal membranes, are recognized by galectins leading to K48- and K63-linked poly-ubiquitination (poly-Ub) of lysosomal proteins followed by recruitment of the macroautophagic/autophagic machinery and degradation.
View Article and Find Full Text PDFJ Cancer
January 2025
Key Laboratory of Molecular Nanostructure and Nanotechnology, CAS Research/Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Science, Beijing 100190, PR China.
Targeted inhibition of mitochondrial oxidative phosphorylation (OXPHOS) complex generation is an emerging and promising cancer treatment strategy, but limited targets and specific inhibitors have been reported. Leucine-rich pentatricopeptide repeat-containing protein (LRPPRC) is an atypical RNA-binding protein that regulates the stability of all 13 mitochondrial DNA-encoded mRNA (mt-mRNA) and thus participates in the synthesis of the OXPHOS complex. LRPPRC is also a prospective therapeutic target for lung adenocarcinoma, serving as a promising target for OXPHOS inhibition.
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