Endocytosed cholesterol must be transferred from the environment (e.g., low-density lipoproteins) via the lysosomal system to the rest of the cell. In Niemann-Pick type C disease, this process fails. In a recent issue of Cell, Kwon et al. (2009) suggest how this transpires mechanistically by crystallizing a domain of a protein defective in this syndrome.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cmet.2009.06.007DOI Listing

Publication Analysis

Top Keywords

niemann-pick type
8
spreading wealth
4
wealth niemann-pick
4
type proteins
4
proteins bind
4
bind transport
4
transport cholesterol
4
cholesterol endocytosed
4
endocytosed cholesterol
4
cholesterol transferred
4

Similar Publications

Maturation of conventional dendritic cells (cDCs) is crucial for maintaining tolerogenic safeguards against auto-immunity and for promoting immunogenic responses to pathogens and cancer. The subcellular mechanism for cDC maturation remains poorly defined. We show that cDCs mature by leveraging an internal reservoir of cholesterol (harnessed from extracellular cell debris and generated by de novo synthesis) to assemble lipid nanodomains on cell surfaces of maturing cDCs, enhance expression of maturation markers and stabilize immune receptor signaling.

View Article and Find Full Text PDF

Acid sphingomyelinase deficiency (ASMD) is a rare, progressive lysosomal storage disorder resulting from a deficiency in acid sphingomyelinase, leading to sphingomyelin accumulation and multi-organ damage. ASMD presents a broad phenotypic spectrum with a continuum of severity, making it challenging to predict the phenotype in very young children and differentiate between acute and chronic neurovisceral disease. No disease-specific treatments existed for ASMD.

View Article and Find Full Text PDF

Sperm activation occurring in both male and female reproductive tract involves a highly complex series of biomolecular dynamics, particularly on membrane lipids and proteins. In mammals, the universal anticipation in cholesterol (CHO) sequestration plays a role in mammalian sperm maturation/capacitation, subsequently enhancing sperm fertilizing ability. In shrimp, we have previously shown that the level of cholesterol (CHO) is significantly reduced in vas deferens sperm when compared with sperm in the testes, presumably due to the sequestering action of the lipid-binding protein, one of which is Niemann-Pick Type C-2 (NPC2).

View Article and Find Full Text PDF

Clinical manifestations and molecular genetics of seven patients with Niemann-Pick type-C: a case series with a novel variant.

J Pediatr Endocrinol Metab

January 2025

Department of Pediatric Metabolism and Ankara University Rare Diseases Application and Research Center, Ankara University Faculty of Medicine, Ankara, Türkiye.

Objectives: Niemann-Pick type C (NPC) is a rare, autosomal recessive, neurodegenerative disorder caused by biallelic pathogenic variants in the or genes, leading to lysosomal lipid accumulation. NPC has an incidence of 1 in 100,000 live births and presents with a wide range of symptoms affecting visceral organs and the central nervous system. We aim to describe the diverse clinical presentations of NPC through case studies.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!