Worcester Foundation for Biomedical Research

About: Worcester Foundation for Biomedical Research is a based out in . It is known for research contribution in the topics: Estrone & Estrogen. The organization has 2195 authors who have published 2646 publications receiving 115809 citations. The organization is also known as: Worcester Foundation for Experimental Biology.

The tip-E Mutation of Drosophila Decreases Saxitoxin Binding and Interacts with Other Mutations Affecting Nerve Membrane Excitability

Abstract: A recessive temperature-sensitive paralytic mutation, tip-E, is associated with reduced binding of [3H]saxitoxin to voltage-sensitive sodium channels in membranes from adult Drosophila heads. There is a decrease of 30-40% in the number of [3H]saxitoxin-binding sites per mg protein (Bmax), but the dissociation constant (Kd) for [3H]saxitoxin binding is normal in the remaining population of binding sites. This decrease is not due to a general hypotrophy of neural tissue since the number of alpha-bungarotoxin binding sites is normal in tip-E mutants. Although saxitoxin binding is reduced in vitro, pharmacological experiments suggest that tip-E mutants have close to the wild-type number of sodium channels in vivo. This suggestion is supported by the observation that at permissive temperatures tip-E only marginally suppresses a mutation which causes enhanced membrane excitability. However, even at permissive temperatures tip-E interacts synergistically with mutations that decrease membrane excitability. In this case, the double mutants exhibit reduced viability and/or longevity. We postulate that either the structure of sodium channels or their microenvironment is altered in tip-E mutants resulting in an increased liability of binding sites in vitro.

A high molecular mass non-muscle tropomyosin isoform stimulates retrograde organelle transport

Abstract: Although non-muscle tropomyosins (TM) have been implicated in various cellular functions, such as stabilization of actin filaments and possibly regulation of organelle transport, their physiological role is still poorly understood. We have probed the role of a high molecular mass isoform of human fibroblast TM, hTM3, in regulating organelle transport by microinjecting an excess amount of bacterially-expressed protein into normal rat kidney (NRK) epithelial cells. The microinjection induced the dramatic retrograde translocation of organelles into the perinuclear area. Microinjection of hTM5, a low molecular mass isoform had no effect on organelle distribution. Fluorescent staining indicated that hTM3 injection stimulated the retrograde movement of both mitochondria and lysosomes. Moreover, both myosin I and cytoplasmic dynein were found to redistribute with the translocated organelles to the perinuclear area, indicating that these organelles were able to move along both microtubules and actin filaments. The involvement of microtubules was further suggested by the partial inhibition of hTM3-induced organelle movement by the microtubule-depolymerizing drug nocodazole. Our results, along with previous genetic and antibody microinjection studies, suggest that hTM3 may be involved in the regulation of organelle transport.

Isolated neurosecretory nerve endings as a tool for studying the mechanism of stimulus-secretion coupling.

Abstract: In the present paper we discuss the properties of a recently developed preparation of isolated neurosecretory nerve endings obtained from the rate neurohypophysis. These nerve terminals release two neurohormones, oxytocin and vasopressin, which are easily assayed by radioimmunoassay. Depolarization-induced secretion is dependent on the same parameters as those regulating release from the whole neural lobe. The isolated nerve endings can be permeabilized by means of digitonin; a treatment which gives direct access to the cytoplasm allowing the study of the minimal requirements for inducing neuropeptide release. Furthermore, some nerve endings are large enough to allow the use of the patch-clamp technique. In the present paper we present evidences which show that the isolated neurohypophysial nerve terminals represent a protent tool for studying the mechanism of stimulus-secretion.