Dictyostelium cells are genetically haploid and therefore easily analyzed for mutant phenotypes. In the past, many tools and molecular markers have been developed for a quantitative and qualitative analysis of the endocytic pathway in these amoebae. This review outlines parallels and discrepancies between mutants in Dictyostelium, the corresponding mammalian cells and the symptoms of human patients affected by lysosomal and trafficking defects. Situations where knowledge from Dictyostelium may potentially help understand human disease and vice versa are also addressed.
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http://dx.doi.org/10.1016/j.semcdb.2010.11.001 | DOI Listing |
Sci Adv
January 2025
Department of Biochemistry Cell and Systems Biology, Institute of Systems, Molecular and Integrative Biology, University of Liverpool, Liverpool, UK.
Lysosomal pH dysregulation is a critical element of the pathophysiology of neurodegenerative diseases, cancers, and lysosomal storage disorders (LSDs). To study the role of lysosomes in pathophysiology, probes to analyze lysosomal size, positioning, and pH are indispensable tools. Here, we developed and characterized a ratiometric genetically encoded lysosomal pH probe, RpH-ILV, targeted to a subpopulation of lysosomal intraluminal vesicles.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Shenzhen Bay Laboratory, Shenzhen, Guandong, China.
Background: The classic mode of STING activation is through binding the cyclic dinucleotide 2'3'-cyclic GMP-AMP (cGAMP), produced by the DNA sensor cyclic GMP-AMP synthase (cGAS), which is important for the innate immune response to microbial infection and autoimmune disease. Modes of STING activation that are independent of cGAS are much less well understood. We wanted to explore the interactome of STING on the organelles during its trafficking route and to understand the regulatory network of STING signaling.
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December 2024
University of Alabama at Birmingham, Birmingham, AL, USA.
Progranulin is a secreted pro-protein that is necessary for maintaining lysosomal function and exerts anti-inflammatory and neurotrophic effects in the brain. Loss-of-function GRN mutations, most of which cause progranulin haploinsufficiency, are a major autosomal dominant cause of frontotemporal dementia (FTD). Other GRN variants are associated with risk for FTD, Alzheimer's disease (AD) and Parkinson's disease.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
Background: Dysregulation of endolysosomal trafficking is a major pathogenic mechanism in Alzheimer's disease (AD). From the family of AD-linked endosomal pathway genes, SORL1 stands out as one of the highest risk factors. SORL1 encodes an endocytic sorting receptor that mediates endosomal trafficking and processing of key AD-associated molecules, including pathogenic forms of amyloid-β (e.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
University of Western Ontario, London, ON, Canada.
Background: Previously, we identified macropinocytosis as a novel mechanism for direct and rapid trafficking of cell surface APP to lysosomes, bypassing early and late endosomes. This process depends on the activity of Arf6 and several Rho-GTPases, and inhibition of macropinocytosis reduces amyloid-beta (Aβ) production. Macropinocytosis is relatively unstudied in neurons and neuronal cells.
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