Protein Sorting in Healthy and Diseased Photoreceptors

2019 ◽  
Vol 5 (1) ◽  
pp. 73-98 ◽  
Author(s):  
Yoshikazu Imanishi
Keyword(s):  
Signal Transduction ◽  
Membrane Protein ◽  
Outer Segment ◽  
Protein Sorting ◽  
Rods And Cones ◽  
Retinal Photoreceptor ◽  
Photoreceptor Neurons ◽  
Cellular Compartments ◽  
G Protein Coupled ◽  
Distinct Membrane

Rods and cones are retinal photoreceptor neurons required for our visual sensation. Because of their highly polarized structures and well-characterized processes of G protein–coupled receptor–mediated phototransduction signaling, these photoreceptors have been excellent models for studying the compartmentalization and sorting of proteins. Rods and cones have a modified ciliary compartment called the outer segment (OS) as well as non-OS compartments. The distinct membrane protein compositions between OS and non-OS compartments suggest that the OS is separated from the rest of the cellular compartments by multiple barriers or gates that are selectively permissive to specific cargoes. This review discusses the mechanisms of protein sorting and compartmentalization in photoreceptor neurons. Proper sorting and compartmentalization of membrane proteins are required for signal transduction and transmission. This review also discusses the roles of compartmentalized signaling, which is compromised in various retinal ciliopathies.

scholarly journals Leukocyte response integrin and integrin-associated protein act as a signal transduction unit in generation of a phagocyte respiratory burst.

1993 ◽  
Vol 178 (4) ◽  
pp. 1165-1174 ◽  
Author(s):  
M Zhou ◽  
E J Brown
Keyword(s):  
Signal Transduction ◽  
Membrane Protein ◽  
Respiratory Burst ◽  
Kinase Inhibitors ◽  
Solid Phase ◽  
Enhanced Sensitivity ◽  
Basement Membrane Protein ◽  
Coated Surfaces ◽  
Leukocyte Response ◽  
Distinct Membrane

The leukocyte response integrin (LRI) is a phagocyte integrin which recognizes the basement membrane protein entactin and the synthetic peptide Lys-Gly-Ala-Gly-Asp-Val (KGAGDV). The function of LRI is intimately associated with that of a distinct membrane protein, integrin-associated protein (IAP), as antibodies which recognizes IAP can inhibit all known functions of LRI. When adherent to surface, the LRI ligands entactin and KGAGDV activate the respiratory burst in polymorphonuclear leukocytes (PMN) and monocytes, as do monoclonal antibodies (mAb) directed at either LRI or IAP. When added in solution, peptides and antibodies specific for LRI, and some, but not all, anti-IAP antibodies, can inhibit the respiratory burst activated by any of these surface-adherent ligands. Only monoclonal anti-IAP antibodies which can inhibit LRI function when added in solution are competent to activate the respiratory burst when adherent to a surface. KGAGDV peptide and anti-LRI added in solution can inhibit anti-IAP-stimulated respiratory burst. The LRI-IAP-initiated respiratory burst is independent of CD18, as judged by: (a) blockade of inhibition by anti-CD18 mAb with the protein kinase A inhibitor HA1004; (b) enhanced sensitivity of CD18-dependent respiratory burst compared with LRI/IAP-dependent respiratory burst to the tyrosine kinase inhibitors genestein and herbimicin; and (c) generation of a respiratory burst in response to KGAGDV, anti-LRI, and anti-IAP coated surfaces in PMN from a patient with LAD. Despite its apparent CD18 independence, LRI/IAP-initiated respiratory burst requires a solid phase ligand and is sensitive to cytochalasin B. These data suggest a model in which LRI and IAP act together as a single signal transduction unit to activate the phagocyte respiratory burst, in a manner that requires CD18-independent cell adhesion.

The spectrin-based membrane skeleton as a membrane protein-sorting machine

1996 ◽  
Vol 270 (5) ◽  
pp. C1263-C1270 ◽  
Author(s):  
K. A. Beck ◽  
W. J. Nelson
Keyword(s):  
Membrane Proteins ◽  
Membrane Protein ◽  
Cell Function ◽  
Protein Sorting ◽  
Membrane Skeleton ◽  
Membrane Domains ◽  
Sorting Machine ◽  
Membrane Compartments ◽  
Molecular Machinery ◽  
Distinct Membrane

Normal cell function is dependent on the existence of membrane compartments that have unique populations of membrane proteins. Sorting of membrane proteins forms the basis for the biogenesis of distinct membrane compartments. There are many examples of membrane protein-sorting events in cells, but the molecular machinery involved is poorly understood. We discuss characteristics of a putative membrane protein-sorting machine and show that the spectrin-based membrane skeleton conforms to these characteristics. The spectrin-based membrane skeleton is a submembranous, spatially limited, two-dimensional lattice that binds a subset of membrane proteins. These properties allow the membrane skeleton to facilitate the formation of distinct membrane domains and thus reveal its potential as a membrane protein-sorting machine.

scholarly journals Every Detail Matters. That Is, How the Interaction between Gα Proteins and Membrane Affects Their Function

Membranes ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 222
Author(s):  
Agnieszka Polit ◽  
Paweł Mystek ◽  
Ewa Błasiak
Keyword(s):  
Signal Transduction ◽  
G Protein ◽  
G Proteins ◽  
Lipid Membranes ◽  
Signaling Proteins ◽  
Heterotrimeric G Proteins ◽  
Membrane Attachment ◽  
The Individual ◽  
Multicellular Organisms ◽  
G Protein Coupled

In highly organized multicellular organisms such as humans, the functions of an individual cell are dependent on signal transduction through G protein-coupled receptors (GPCRs) and subsequently heterotrimeric G proteins. As most of the elements belonging to the signal transduction system are bound to lipid membranes, researchers are showing increasing interest in studying the accompanying protein–lipid interactions, which have been demonstrated to not only provide the environment but also regulate proper and efficient signal transduction. The mode of interaction between the cell membrane and G proteins is well known. Despite this, the recognition mechanisms at the molecular level and how the individual G protein-membrane attachment signals are interrelated in the process of the complex control of membrane targeting of G proteins remain unelucidated. This review focuses on the mechanisms by which mammalian Gα subunits of G proteins interact with lipids and the factors responsible for the specificity of membrane association. We summarize recent data on how these signaling proteins are precisely targeted to a specific site in the membrane region by introducing well-defined modifications as well as through the presence of polybasic regions within these proteins and interactions with other components of the heterocomplex.

Caffeine does not inhibit substance P-evoked intracellular Ca2+ mobilization in rat salivary acinar cells

1999 ◽  
Vol 276 (4) ◽  
pp. C915-C922 ◽  
Author(s):  
J. T. Seo ◽  
H. Sugiya ◽  
S. I. Lee ◽  
M. C. Steward ◽  
A. C. Elliott
Keyword(s):  
Signal Transduction ◽  
Substance P ◽  
G Protein ◽  
Acinar Cells ◽  
Inhibitory Effect ◽  
Structural Motif ◽  
Stimulus Response ◽  
Inhibit Substance ◽  
Prior Application ◽  
G Protein Coupled

We used the Ca2+-sensitive fluorescent dye fura 2, together with measurements of intracellulard- myo-inositol 1,4,5-trisphosphate [Ins(1,4,5) P 3], to assess the inhibitory effects of caffeine on signal transduction via G protein-coupled receptor pathways in isolated rat mandibular salivary acinar cells. ACh, norepinephrine (NE), and substance P (SP) all evoked substantial increases in the intracellular free Ca2+ concentration ([Ca2+]i). Responses to ACh and NE were markedly inhibited by prior application of 20 mM caffeine. The inhibitory effect of caffeine was not reproduced by phosphodiesterase inhibition with IBMX or addition of cell-permeant dibutyryl cAMP. In contrast to the ACh and NE responses, the [Ca2+]iresponse to SP was unaffected by caffeine. Despite this, SP and ACh appeared to mobilize Ca2+ from a common intracellular pool. Measurements of agonist-induced changes in Ins(1,4,5) P 3levels confirmed that caffeine inhibited the stimulus-response coupling pathway at a point before Ins(1,4,5) P 3generation. Caffeine did not, however, inhibit [Ca2+]iresponses evoked by direct activation of G proteins with 40 mM F−. These data show that caffeine inhibits G protein-coupled signal transduction in these cells at some element that is common to the muscarinic and α-adrenergic signaling pathways but is not shared by the SP signaling pathway. We suggest that this element might be a specific structural motif on the G protein-coupled muscarinic and α-adrenergic receptors.

scholarly journals Vitamin E-based glycoside amphiphiles for membrane protein structural studies

2018 ◽  
Vol 16 (14) ◽  
pp. 2489-2498 ◽  
Author(s):  
Muhammad Ehsan ◽  
Yang Du ◽  
Iago Molist ◽  
Alpay B. Seven ◽  
Parameswaran Hariharan ◽  
...  
Keyword(s):  
Vitamin E ◽  
Membrane Protein ◽  
G Protein ◽  
Structural Studies ◽  
G Protein Coupled Receptor ◽  
G Protein Coupled ◽  
Novel Agent

A vitamin E-based novel agent (i.e., VEG-3) was markedly effective at stabilizing and visualizing a G-protein coupled receptor (GPCR)-Gs complex.

scholarly journals Correlation between brain volume and retinal photoreceptor outer segment volume in normal aging and neurodegenerative diseases

PLoS ONE ◽  
2020 ◽  
Vol 15 (9) ◽  
pp. e0237078
Author(s):  
Atsuro Uchida ◽  
Jagan A. Pillai ◽  
Robert Bermel ◽  
Stephen E. Jones ◽  
Hubert Fernandez ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Outer Segment ◽  
Brain Volume ◽  
Normal Aging ◽  
Photoreceptor Outer Segment ◽  
Retinal Photoreceptor ◽  
Segment Volume

scholarly journals Regulation of nephron water and electrolyte transport by adenylyl cyclases

2014 ◽  
Vol 306 (7) ◽  
pp. F701-F709 ◽  
Author(s):  
Timo Rieg ◽  
Donald E. Kohan
Keyword(s):  
Hormonal Regulation ◽  
Electrolyte Transport ◽  
Adenylyl Cyclases ◽  
Disease Pathogenesis ◽  
Membrane Bound ◽  
G Protein Coupled ◽  
Camp Formation ◽  
Distinct Membrane ◽  
Genetically Modified Animals

Adenylyl cyclases (AC) catalyze formation of cAMP, a critical component of G protein-coupled receptor signaling. So far, nine distinct membrane-bound AC isoforms (AC1-9) and one soluble AC (sAC) have been identified and, except for AC8, all of them are expressed in the kidney. While the role of ACs in renal cAMP formation is well established, we are just beginning to understand the function of individual AC isoforms, particularly with regard to hormonal regulation of transporter and channel phosphorylation, membrane abundance, and trafficking. This review focuses on the role of different AC isoforms in regulating renal water and electrolyte transport in health as well as potential pathological implications of disordered AC isoform function. In particular, we focus on modulation of transporter and channel abundance, activity, and phosphorylation, with an emphasis on studies employing genetically modified animals. As will be described, it is now evident that specific AC isoforms can exert unique effects in the kidney that may have important implications in our understanding of normal physiology as well as disease pathogenesis.

Sign in / Sign up

Export Citation Format

Share Document