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Biomedical subjects

M Sheetz

Publications and source records attributed to M Sheetz.

10 recordsLinked to original sources
PubMed2001

Rap1 is involved in cell stretching modulation of p38 but not ERK or JNK MAP kinase.

Mechanical force or mechanical stress modulates intracellular signal pathways, including the mitogen-activated protein kinase (MAP kinase) cascades. In our system, cell stretching activated and cell contraction inactivated all three MAP kinase pathways (MKK1/2-extracellular signal-regulated kinase (ERK), MKK4 (SEK1)-cJun N-terminal kinase (JNK) and MKK3/6-p38 pathways). However, little is known about the molecular mechanisms that link the mechanical force to the MAP kinase cascades. To test whether Ras and Rap1 are possible components in the stretch-activated MAP kinase pathways, we examined if Ras and Rap1 were activated by cell stretching and if inhibition of their activity decreased the stretch-enhanced MAP kinase activity. Rap1 was activated by cell stretching and inactivated by cell contraction, whereas Ras was inactivated by cell stretching and activated by cell contraction. Rap1GapII and SPA-1, downregulators of Rap1 activity, decreased the stretch-enhanced p38 activity, whereas a dominant-negative mutant of Ras (RasN17) did not inhibit the stretch-initiated activation of MAP kinases. Furthermore, overexpression of Rap1 enhanced p38 activity but not ERK or JNK activity. These results indicate that Rap1 is involved in transducing the stretch-initiated signal to the MKK3/6-p38 pathway, but not to the MEK1/2-ERK or the MKK4 (SEK1)/MKK7-JNK pathway. Thus, Rap1 plays a unique role in force-initiated signal transduction.

Animals↗
PubMed1998

First one in, last one out: the role of gabaergic transmission in generation and degeneration.

This paper is the result of discussions between scientists working in widely separated areas, united by an interest in the hippocampus. The discussions focused on the possible role of GABA in the development and maturation of the hippocampus and in neurodegeneration in Alzheimer's disease (AD). GABA neurons are among the first to differentiate in the hippocampus and the properties of GABA neurotransmission in the developing hippocampus are distinct from those in the adult. GABAergic transmission may play a role in the clustering and maturation of GABA receptors, as well as of receptors for other neurotransmitters. The development and maturation of synaptic connections involves changes in the organization of the cytoskeleton, and mechanical force generation is probably required to establish appropriate points of contact. This generation of force may require coupling of specific receptors to the cytoskeleton through specialized proteins. In AD, much of the developmental process is progressively unraveled in the hippocampus, as afferent fibers, most notably from entorhinal excitatory neurons and from basal forebrain cholinergic cells, degenerate. This denervation undoubtedly has consequences for receptor systems, dendritic morphology and the underlying cytoskeleton. GABA neurons remain in the AD hippocampus, and may actually contribute to abnormal firing and degeneration of remaining pyramidal neurons. This attempt to bring together data from different areas of research has allowed the development of a scheme which identifies significant specific gaps in our knowledge, which could be readily filled by focused experimental work.

Animals↗
PubMed1993

Fast axonal transport is required for growth cone advance.

Growth cones are capable of advancing despite linkage to a stationary axonal cytoskeleton in chick and murine dorsal root ganglion neurites. Several lines of evidence point to the growth cone as the site of cytoskeletal elongation. Fast axonal transport is probably the means by which cytoskeletal elements or cofactors are rapidly moved through the axon. We report that direct, but reversible, inhibition of fast axonal transport with laser optical tweezers inhibits growth cone motility if cytoskeletal attachment to the cell body is maintained. Advancement ceases after a distance-dependent lag period which correlates with the rate of fast axonal transport. But severing the axonal cytoskeleton with the laser tweezers allows growth cones to advance considerably further. We suggest that axon elongation requires fast axonal transport but growth cone motility does not.

Animals↗
PubMed1980

Reduced chronic hemolysis during high-dose vitamin E administration in Mediterranean-type glucose-6-phosphate dehydrogenase deficiency.

The observation that high-dose oral vitamin E supplementation (800 IU per day) improved red-cell survival in two rare disorders associated with increased red-cell susceptibility to oxidative stress prompted a similar trial in 23 patients with Mediterranean glucose-6-phosphate dehydrogenase (G6PD) deficiency. Three months of vitamin E administration resulted in decreased chronic hemolysis as evidenced by improved red-cell life span (P less than 0.025), with an improvement in red-cell half-life from 22.9 +/- 0.7 days to 25.1 +/- 0.6 days (mean +/- S.E.M.), increased hemoglobin concentration (P less than 0.001), and decreased reticulocytosis (P less than 0.001) as compared with base-line values. Evaluation after one year of vitamin E administration demonstrated sustained improvement in all these indexes. Controlled clinical trials of vitamin E supplementation may be warranted to examine its efficacy in ameliorating acute hemolytic crises or in reducing morbidity from neonatal jaundice in this relatively common genetic disorder.

Administration, Oral↗
PubMed1975

Detection and ultrastructural localization of human smooth muscle myosin-like molecules in human non-muscle cells by specific antibodies.

Spectrin, a protein complex which is peripherally attached to the cytoplasmic surface of the human erythrocyte membrane, cannot be detected (by complement fixation with anti-spectrin antibodies) in homogenates of several different human non-muscle cells studied. On the other hand, a protein antigenically identical or similar to human smooth muscle myosin was detected (by complement fixation with antibodies to uterine smooth muscle myosin) in these cells. In the case of human fibroblast line WI38, this smooth muscle myosin like component was shown (by ferritin-antibody experiments in electron microscopy) to be at least partly associated with cytoplasmic surface of the plasma membrane of the cell. It is proposed that the spectrin complex of the erythrocyte membrane and the smooth muscle myosin-like component of the fibroblast membrane play similar roles in regulating the translational mobilities of integral proteins in their respective membranes.

Antigen-Antibody Reactions↗
PubMed1970

On the interactions of lipids and proteins in the red blood cell membrane.

The effects of temperature and of the action of a purified phospholipase C enzyme preparation on human red blood cell membranes has been investigated by chemical analyses, circular dichroism, and proton magnetic resonance measurements. The results indicate that a substantial fraction of the phospholipids and the proteins of the membranes can change structure independently of one another, suggesting a mosaic pattern for the organization of the lipids and proteins in membranes.

Cell Membrane↗