Intracellular Signalling Involved in Volume Regulatory Decrease

AbstractThe use of exosomes in clinical settings is progressively becoming a reality, as clinical trials testing exosomes for diagnostic and therapeutic applications are generating remarkable interest from the scientific community and investors. Exosomes are small extracellular vesicles secreted by all cell types playing intercellular communication roles in health and disease by transferring cellular cargoes such as functional proteins, metabolites and nucleic acids to recipient cells. An in-depth understanding of exosome biology is therefore essential to ensure clinical development of exosome based investigational therapeutic products. Here we summarise the most up-to-date knowkedge about the complex biological journey of exosomes from biogenesis and secretion, transport and uptake to their intracellular signalling. We delineate the major pathways and molecular players that influence each step of exosome physiology, highlighting the routes of interest, which will be of benefit to exosome manipulation and engineering. We highlight the main controversies in the field of exosome research: their adequate definition, characterisation and biogenesis at plasma membrane. We also delineate the most common identified pitfalls affecting exosome research and development. Unravelling exosome physiology is key to their ultimate progression towards clinical applications.

Water permeability of apical and basolateral cell membranes of rat inner medullary collecting duct

AJP Renal Physiology ◽

10.1152/ajprenal.1990.259.6.f986 ◽

1990 ◽

Vol 259 (6) ◽

pp. F986-F999 ◽

Cited By ~ 5

Author(s):

B. Flamion ◽

K. R. Spring

Keyword(s):

Water Flow ◽

Water Permeability ◽

Cell Membranes ◽

Apical Membrane ◽

Collecting Duct ◽

Basolateral Membrane ◽

Volume Regulatory Decrease ◽

Water Permeation ◽

Inner Medullary Collecting Duct ◽

Medullary Collecting Duct

To quantify the pathways for water permeation through the kidney medulla, knowledge of the water permeability (Posmol) of individual cell membranes in inner medullary collecting duct (IMCD) is required. Therefore IMCD segments from the inner two thirds of inner medulla of Sprague-Dawley rats were perfused in vitro using a setup devised for rapid bath and luminal fluid exchanges (half time, t1/2, of 55 and 41 ms). Differential interference contrast microscopy, coupled to video recording, was used to measure volume and approximate surface areas of single cells. Volume and volume-to-surface area ratio of IMCD cells were strongly correlated with their position along the inner medullary axis. Transmembrane water flow (Jv) was measured in response to a variety of osmotic gradients (delta II) presented on either basolateral or luminal side of the cells. The linear relation between Jv and delta II yielded the cell membrane Posmol, which was then corrected for membrane infoldings. Basolateral membrane Posmol was 126 +/- 3 microns/s. Apical membrane Posmol rose from a basal value of 26 +/- 3 microns/s to 99 +/- 5 microns/s in presence of antidiuretic hormone (ADH). Because of amplification of basolateral membrane, the ADH-stimulated apical membrane remained rate-limiting for transcellular osmotic water flow, and the IMCD cell did not swell significantly. Calculated transcellular Posmol, expressed in terms of smooth luminal surface, was 64 microns/s without ADH and 207 microns/s with ADH. IMCD cells in anisosmotic media displayed almost complete volume regulatory decrease but only partial volume regulatory increase.

Novel treatment of excitotoxicity: targeted disruption of intracellular signalling from glutamate receptors

Biochemical Pharmacology ◽

10.1016/s0006-2952(03)00297-1 ◽

2003 ◽

Vol 66 (6) ◽

pp. 877-886 ◽

Cited By ~ 55

Author(s):

Michelle M Aarts ◽

Michael Tymianski

Keyword(s):

Glutamate Receptors ◽

Intracellular Signalling ◽

Targeted Disruption ◽

Novel Treatment

Intracellular signalling as a parallel distributed process

Journal of Theoretical Biology ◽

10.1016/s0022-5193(05)80268-1 ◽

1990 ◽

Vol 143 (2) ◽

pp. 215-231 ◽

Cited By ~ 90

Author(s):

D. Bray

Keyword(s):

Intracellular Signalling ◽

Distributed Process

Calcium receptor-mediated intracellular signalling

Cell Calcium ◽

10.1016/j.ceca.2003.10.017 ◽

2004 ◽

Vol 35 (3) ◽

pp. 217-228 ◽

Cited By ~ 113

Author(s):

Donald T Ward

Keyword(s):

Intracellular Signalling ◽

Calcium Receptor

Breast cancer and sphingolipid signalling

Journal of Dairy Research ◽

10.1017/s0022029905001238 ◽

2005 ◽

Vol 72 (S1) ◽

pp. 5-13 ◽

Cited By ~ 2

Author(s):

Paola Signorelli ◽

Riccardo Ghidoni

Keyword(s):

Breast Cancer ◽

Cancer Prevention ◽

Biological Membranes ◽

Breast Cancer Prevention ◽

Intracellular Signalling ◽

Regulated Functions ◽

Tumour Initiation ◽

Prevention And Therapy

Cancer develops from overlapping events that tend to deregulate the metabolism and unbalance the homeostasis of cells. Sphingolipids, major components of biological membranes, are also mediators of intracellular signalling. Their metabolism can be influenced by diverse stimuli and the accumulation or deficiency of intermediates may trigger proliferation and/or impair the ability of damaged cells to undergo apoptosis. Many sphingolipid-regulated functions are implicated in tumour initiation, promotion, progression and responsiveness to chemotherapy. In this review, evidence of the alteration of sphingolipids metabolism and signalling will be discussed in breast cancer prevention and therapy.