Biomedical subjects

Jean Gruenberg

Publications and source records attributed to Jean Gruenberg.

22 records · Page 2Linked to original sources

PubMed2002

Separation and characterization of late endosomal membrane domains.

Very little is known about the biophysical properties and the lipid or protein composition of membrane domains presumably present in endocytic and biosynthetic organelles. Here we analyzed the membrane composition of late endosomes by suborganellar fractionation in the absence of detergent. We found that the internal membranes of this multivesicular organelle can be separated from the limiting membrane and that each membrane population exhibited a defined composition. Our data also indicated that internal membranes may consist of at least two populations, containing primarily phosphatidylcholine or lysobisphosphatidic acid as major phospholipid, arguing for the existence of significant microheterogeneity within late endosomal membranes. We also found that lysobisphosphatidic acid exhibited unique pH-dependent fusogenic properties, and we speculated that this lipid is an ideal candidate to regulate the dynamic properties of this internal membrane mosaic.

Animals↗

PubMed2002

Late endosome motility depends on lipids via the small GTPase Rab7.

We report that lipids contribute to regulate the bidirectional motility of late endocytic compartments. Late endocytic vesicles loaded with cholesterol lose their dynamic properties, and become essentially immobile, including in cells from Niemann-Pick C patients. These vesicles then retain cytoplasmic dynein activity, but seem to be unable to acquire kinesin activity, eventually leading to paralysis. Our data suggest that this defect depends on the small GTPase Rab7, since the motility of vesicles loaded with cholesterol can be restored by the Rab7 inhibitory mutant N125I. Conversely, wild-type Rab7 overexpression mimics the effects of cholesterol on motility in control cells. Consistently, cholesterol accumulation increases the amounts of membrane-associated Rab7, and inhibits Rab7 membrane extraction by the guanine nucleotide dissociation inhibitor. Our observations thus indicate that cholesterol contributes to regulate the Rab7 cycle, and that Rab7 in turn controls the net movement of late endocytic elements. We conclude that motor functions can be regulated by the membrane lipid composition via the Rab7 cycle.

Androstenes↗

PubMed2002

Oiling the wheels of the endocytic pathway.

An ever more complete picture of the organization and function of the endocytic pathway is emerging. New mechanisms, and in particular lipid-based mechanisms that couple membrane dynamics and sorting, are being unraveled. But the final picture is still coming into focus as new membrane domains, cell entry pathways and compartments come into view. Of special interest are the recent findings that pathogenic agents, in contrast to scientists, seem to have long discovered how to subvert membrane specialization to their own advantage.

Animals↗

PubMed2002

Signaling from the far side.

Signaling by cell surface receptors is often turned off by receptor endocytosis and downregulation. However, it appears that some signaling pathways continue to fire from within cells. A recent study now suggests that a late endosomal p14/MP1-MAPK scaffold complex is critical for the ERK signaling pathway.

Animals↗