StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis

Rodríguez‐Agudo, Daniel; Malacrida, Leonel; Kakiyama, Genta; Sparrer, Tavis; Fortes, Carolina; Maceyka, Michael; Subler, Mark A.; Windle, Jolene J.; Gratton, Enrico; Pandak, William M.; Gil, Gregorio

doi:10.1194/jlr.m091967

Cited by 29 publications

(27 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, a 1.3-Mb inversion in greater horseshoe bat chromosome 28 (homologous to 29.5 Mb of human chromosome 15; Extended Data Fig. 12a ) disrupted STARD5 , a gene involved in cholesterol homeostasis in liver cells 54 . The rearrangement separated exons 1–5 from exon 6, and disrupted splicing of the transcripts (Extended Data Fig.…”

Section: Chromosomal Evolutionmentioning

confidence: 99%

Towards complete and error-free genome assemblies of all vertebrate species

Rhie

McCarthy

Fédrigo

et al. 2021

Nature

1,490

671

View full text Add to dashboard Cite

High-quality and complete reference genome assemblies are fundamental for the application of genomics to biology, disease, and biodiversity conservation. However, such assemblies are available for only a few non-microbial species1–4. To address this issue, the international Genome 10K (G10K) consortium5,6 has worked over a five-year period to evaluate and develop cost-effective methods for assembling highly accurate and nearly complete reference genomes. Here we present lessons learned from generating assemblies for 16 species that represent six major vertebrate lineages. We confirm that long-read sequencing technologies are essential for maximizing genome quality, and that unresolved complex repeats and haplotype heterozygosity are major sources of assembly error when not handled correctly. Our assemblies correct substantial errors, add missing sequence in some of the best historical reference genomes, and reveal biological discoveries. These include the identification of many false gene duplications, increases in gene sizes, chromosome rearrangements that are specific to lineages, a repeated independent chromosome breakpoint in bat genomes, and a canonical GC-rich pattern in protein-coding genes and their regulatory regions. Adopting these lessons, we have embarked on the Vertebrate Genomes Project (VGP), an international effort to generate high-quality, complete reference genomes for all of the roughly 70,000 extant vertebrate species and to help to enable a new era of discovery across the life sciences.

show abstract

Section: Chromosomal Evolutionmentioning

confidence: 99%

Towards complete and error-free genome assemblies of all vertebrate species

Rhie

McCarthy

Fédrigo

et al. 2021

Nature

1,490

671

View full text Add to dashboard Cite

show abstract

“…Soluble lipid transfer proteins (LTPs) such as NPC2 and the START family facilitate the bidirectional equilibration of sterols down their chemical activity gradients 36,72‐75 . Such transporters not only have binding pockets for their substrates but also often deploy basic residues for electrostatic membrane docking and hydrophobic side chains for bilayer insertion at relevant donor and acceptor sites 68 .…”

Section: Intracellular Cholesterol Transportmentioning

confidence: 99%

Active cholesterol 20 years on

Lange

Steck

2020

Traffic

View full text Add to dashboard Cite

This review considers the following hypotheses, some well‐supported and some speculative. Almost all of the sterol molecules in plasma membranes are associated with bilayer phospholipids in complexes of varied strength and stoichiometry. These complexes underlie many of the material properties of the bilayer. The small fraction of cholesterol molecules exceeding the binding capacity of the phospholipids is thermodynamically active and serves diverse functions. It circulates briskly among the cell membranes, particularly through contact sites linking the organelles. Active cholesterol provides the upstream feedback signal to multiple mechanisms governing plasma membrane homeostasis, pegging the sterol level to a threshold set by its phospholipids. Active cholesterol could also be the cargo for various inter‐organelle transporters and the form excreted from cells by reverse transport. Furthermore, it is integral to the function of caveolae; a mediator of Hedgehog regulation; and a ligand for the binding of cytolytic toxins to membranes. Active cholesterol modulates a variety of plasma membrane proteins—receptors, channels and transporters—at least in vitro.

show abstract

“…STARD5 has been shown to mediate cholesterol transport between liposomes and between plasma membrane and endoplasmic reticulum (ER). In the same study deletion of STARD5 in mice resulted in reduced plasma membrane cholesterol, lipid accumulation but unaltered cholesterol levels intracellularly in macrophages (which express STARD5) [ 36 ]. In addition, STARD5 seems also important for bile acid transportation [ 8 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of Two Novel Variants of the Steroidogenic Acute Regulatory Protein Identified in a Girl with Classic Lipoid Congenital Adrenal Hyperplasia

Katharopoulos

Iorgi

Fernández-Álvarez

et al. 2020

IJMS

View full text Add to dashboard Cite

Congenital adrenal hyperplasia (CAH) consists of several autosomal recessive disorders that inhibit steroid biosynthesis. We describe a case report diagnosed with adrenal insufficiency due to low adrenal steroids and adrenocorticotropic hormone excess due to lack of cortisol negative feedback signaling to the pituary gland. Genetic work up revealed two missense variants, p.Thr204Arg and p.Leu260Arg in the STAR gene, inherited by both parents (non-consanguineous). The StAR protein supports CYP11A1 enzyme to cleave the side chain of cholesterol and synthesize pregnenolone which is metabolized to all steroid hormones. We used bioinformatics to predict the impact of the variants on StAR activity and then we performed functional tests to characterize the two novel variants. In a cell system we tested the ability of variants to support cholesterol conversion to pregnenolone and measured their mRNA and protein expression. For both variants, we observed loss of StAR function, reduced protein expression and categorized them as pathogenic variants according to guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. These results fit the phenotype of the girl during diagnosis. This study characterizes two novel variants and expands the list of missense variants that cause CAH.

show abstract

StarD5: an ER stress protein regulates plasma membrane and intracellular cholesterol homeostasis

Cited by 29 publications

References 68 publications

Towards complete and error-free genome assemblies of all vertebrate species

Towards complete and error-free genome assemblies of all vertebrate species

Active cholesterol 20 years on

Characterization of Two Novel Variants of the Steroidogenic Acute Regulatory Protein Identified in a Girl with Classic Lipoid Congenital Adrenal Hyperplasia

Contact Info

Product

Resources

About