Biomedical subjects

Tim Levine

Publications and source records attributed to Tim Levine.

6 recordsLinked to original sources

PubMed2006

Receptor activation alters inner surface potential during phagocytosis.

The surface potential of biological membranes varies according to their lipid composition. We devised genetically encoded probes to assess surface potential in intact cells. These probes revealed marked, localized alterations in the charge of the inner surface of the plasma membrane of macrophages during the course of phagocytosis. Hydrolysis of phosphoinositides and displacement of phosphatidylserine accounted for the change in surface potential at the phagosomal cup. Signaling molecules such as K-Ras, Rac1, and c-Src that are targeted to the membrane by electrostatic interactions were rapidly released from membrane subdomains where the surface charge was altered by lipid remodeling during phagocytosis.

Animals↗

PubMed2006

Inter-organelle membrane contact sites: through a glass, darkly.

Inter-organelle membrane contact sites are zones where heterologous membranes, usually the endoplasmic reticulum plus a partner organelle, come into close apposition. These sites are very poorly understood because so few of their components have been identified; however, it is clear that they are specialised for traffic of material and information between the two membranes. There have been recent advances in the study of lipid transfer proteins, such as ceramide transfer protein (CERT) and homologues of oxysterol binding protein (OSBP). Not only can these proteins carry lipids across the cytoplasm, but they have been found to target both the endoplasmic reticulum and a partnering organelle, and in some cases have been localised to membrane contact sites. Further work will be needed to test whether these lipid transfer proteins act when anchored at inter-organelle contact sites.

Animals↗

PubMed2005

A new way for sterols to walk on water.

The crystal structure of a homolog of oxysterol binding protein solved by Jim Hurley and coworkers (Im et al., 2005) shows that this large family acts as cholesterol transporters, taking not only the lipid but also large numbers of water molecules into an internal pocket.

Fungal Proteins↗

PubMed2005

Endoplasmic reticulum: one continuous network compartmentalized by extrinsic cues.

The endoplasmic reticulum (ER) is an extensive three-dimensional network that stretches from the inner nuclear envelope to the cell cortex with a single, continuous membrane and a single, continuous lumen. Yet the ER contains specialized regions that carry out unique functions. The question that immediately arises is how the ER can be compartmentalized if it is continuous, and the answer to this is that cellular landmarks with unique sub-cellular distributions impose non-uniformity on the ER from outside, creating structural and functional sub-domains of the ER.

Animals↗

PubMed2004

SSD: sterol-sensing direct.

Cholesterol homeostasis is established by a complex of three proteins, one of which contains a hydrophobic domain previously termed a sterol-sensing domain. New biochemical studies of this domain demonstrate direct high-affinity binding of the sterol-sensing domain to sterol.

Animals↗

PubMed2004

Short-range intracellular trafficking of small molecules across endoplasmic reticulum junctions.

Intracellular trafficking is not mediated exclusively by vesicles. Additional, non-vesicular mechanisms transport material, in particular small molecules such as lipids and Ca(2+) ions, from one organelle to another. This transport occurs at narrow cytoplasmic gaps called membrane contact sites (MCSs), at which two organelles come into close apposition. Despite the conservation of these structures throughout evolution, little is known about this transport, largely because of a lack of knowledge of almost all molecular components of MCSs. Recently, this situation has started to change because the structural proteins that bridge an MCS are now known in a single case, and proteins implicated in lipid trafficking have been localized to MCSs. In the light of these advances, I hypothesize that the endoplasmic reticulum has a central role in the trafficking of lipids and ions by forming a network of MCSs with most other intracellular organelles.

Animals↗