Kinase-anchoring proteins in ciliary signal transduction

2021 ◽  
Vol 478 (8) ◽  
pp. 1617-1629
Author(s):  
Janani Gopalan ◽  
Linda Wordeman ◽  
John D. Scott
Keyword(s):  
Signal Transduction ◽  
Brownian Motion ◽  
Plasma Membrane ◽  
Primary Cilium ◽  
Regulatory Proteins ◽  
Macromolecular Complexes ◽  
Regulatory Enzymes ◽  
Ciliary Function ◽  
Anchoring Proteins ◽  
Signal Relay

Historically, the diffusion of chemical signals through the cell was thought to occur within a cytoplasmic soup bounded by the plasma membrane. This theory was predicated on the notion that all regulatory enzymes are soluble and moved with a Brownian motion. Although enzyme compartmentalization was initially rebuffed by biochemists as a ‘last refuge of a scoundrel', signal relay through macromolecular complexes is now accepted as a fundamental tenet of the burgeoning field of spatial biology. A-Kinase anchoring proteins (AKAPs) are prototypic enzyme-organizing elements that position clusters of regulatory proteins at defined subcellular locations. In parallel, the primary cilium has gained recognition as a subcellular mechanosensory organelle that amplifies second messenger signals pertaining to metazoan development. This article highlights advances in our understanding of AKAP signaling within the primary cilium and how defective ciliary function contributes to an increasing number of diseases known as ciliopathies.

Review of Progress in Predicting Protein Methylation Sites

2019 ◽  
Vol 23 (15) ◽  
pp. 1663-1670 ◽  
Author(s):  
Chunyan Ao ◽  
Shunshan Jin ◽  
Yuan Lin ◽  
Quan Zou
Keyword(s):  
Gene Expression ◽  
Signal Transduction ◽  
Transcriptional Activity ◽  
Regulation Of Gene Expression ◽  
Protein Methylation ◽  
Biological Processes ◽  
Post Translational Modification ◽  
Regulatory Enzymes ◽  
Lysine Residues ◽  
Arginine Residues

Protein methylation is an important and reversible post-translational modification that regulates many biological processes in cells. It occurs mainly on lysine and arginine residues and involves many important biological processes, including transcriptional activity, signal transduction, and the regulation of gene expression. Protein methylation and its regulatory enzymes are related to a variety of human diseases, so improved identification of methylation sites is useful for designing drugs for a variety of related diseases. In this review, we systematically summarize and analyze the tools used for the prediction of protein methylation sites on arginine and lysine residues over the last decade.

scholarly journals Paracrystalline arrays of membrane-to-membrane cross bridges associated with the inner surface of plasma membrane

1978 ◽  
Vol 77 (2) ◽  
pp. 323-328 ◽  
Author(s):  
WW Franke ◽  
C Grund ◽  
E Schmid ◽  
E Mandelkow
Keyword(s):  
Plasma Membrane ◽  
Plasma Membranes ◽  
Cultured Cells ◽  
Membrane Surface ◽  
Hexagonal Lattice ◽  
Interparticle Distance ◽  
Macromolecular Complexes ◽  
Inner Surface ◽  
Cross Bridges ◽  
Plasma Membrane Surface

In cultured cells of the rat kangaroo PtK2 line, veils of the cell surface were observed which consisted of only plasma membrane and paracrystalline arrays of membrane-associated particles sandwiched in between. These membrane-to-membrane cross-bridging 9-to 11-nm wide particles were somewhat coumellar-shaped and were arranged on a hexagonal lattice with an interparticle distance of 16nm. At higher magnification, they revealed an unstained core, thus suggesting a ringlike substructure. Similar arrays of paracrystal-containing veils, which were rather variable in size and frequency, were also observed in other cultured cells. It is hypothesized that these paracrystals represent protein macromolecular complexes associated with the inner plasma membrane surface which crystallize when plasma membranes come into close intracellular contact and other components of the subsurface network are removed.

scholarly journals Morphological Alterations of CAD Cells Overexpressing AKT1

2020 ◽  
Vol 26 (S2) ◽  
pp. 1354-1358
Author(s):  
James Wachira
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Cell Survival ◽  
Fluorescent Protein ◽  
Morphological Changes ◽  
Protein Localization ◽  
Signal Transduction Pathways ◽  
Morphological Alterations ◽  
Cellular Models ◽  
Cad Cells

AbstractCAD cells are neuronal cells used in studies of cell differentiation and in cellular models of neuropathology. When cultured in differentiation medium, CAD cells exhibit characteristics of mature neurons including the generation of action potential. In addition to being a central signaling kinase in cell survival, AKT1 plays important roles in the nervous system including neuroplasticity and this study examined the localization of exogenous AKT1 in CAD cells. Neuropeptides modulate many signal transduction pathways and melacortins are implicated in regulating growth factor signal transduction pathways, including the PI3K/AKT pathway. AKT1-DsReD was transfected into CAD cells that were stably expressing melanocortin 3-receptor-GFP (MC3R-GFP), a G-protein coupled receptor. The cells were imaged with confocal microscopy to determine the fluorescent protein localization patterns. AKT1-DsRed was predominantly localized in the cytoplasm and the nucleus. Further, expression of exogenous AKT1 in these cell lines led to morphological changes reminiscent of apoptosis. As expected, MC3R-GFP localized to the plasma membrane but it internalized upon cell stimulation with the cognate ligand. In limited areas of the plasma membrane, AKT1-DsRed and MC3R-GFP were colocalized. In conclusion, quantitative studies to understand the role of relative levels of AKT1 in determining cell survival are needed.

scholarly journals Fluorescent, short-chain C6-NBD-sphingomyelin, but not C6-NBD-glucosylceramide, is subject to extensive degradation in the plasma membrane: implications for signal transduction related to cell differentiation

1995 ◽  
Vol 309 (3) ◽  
pp. 905-912 ◽  
Author(s):  
J W Kok ◽  
T Babia ◽  
K Klappe ◽  
D Hoekstra
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Cell Differentiation ◽  
Plasma Membranes ◽  
Cell Types ◽  
Short Chain ◽  
Synthetic Activity ◽  
Intact Cells ◽  
Ht29 Cells ◽  
Extensive Degradation

The involvement of the plasma membrane in the metabolism of the sphingolipids sphingomyelin (SM) and glucosylceramide (GlcCer) was studied, employing fluorescent short-chain analogues of these lipids, 6-[N-(7-nitro-2,1,3-benzoxadiazol-4-yl) amino]hexanoylsphingosylphosphorylcholine (C6-NBD-SM), C6-NBD-GlcCer and their common biosynthetic precursor C6-NBD-ceramide (C6-NBD-Cer). Although these fluorescent short-chain analogues are metabolically active, some caution is to be taken in view of potential changes in biophysical/biochemical properties of the lipid compared with its natural counterpart. However, these short-chain analogues offer the advantage of studying the lipid metabolic enzymes in their natural environment, since detergent solubilization is not necessary for measuring their activity. These studies were carried out with several cell types, including two phenotypes (differing in state of differentiation) of HT29 cells. Degradation and biosynthesis of C6-NBD-SM and C6-NBD-GlcCer were determined in intact cells, in their isolated plasma membranes, and in plasma membranes isolated from rat liver tissue. C6-NBD-SM was found to be subject to extensive degradation in the plasma membrane, due to neutral sphingomyelinase (N-SMase) activity. The extent of C6-NBD-SM hydrolysis showed a general cell-type dependence and turned out to be dependent on the state of cell differentiation, as revealed for HT29 cells. In undifferentiated HT29 cells N-SMase activity was at least threefold higher than in its differentiated counterpart. In contrast, in all cell types studied, very little if any biosynthesis of C6-NBD-SM from the precursor C6-NBD-Cer occurred. Moreover, in the case of C6-NBD-GlcCer, neither hydrolytic nor synthetic activity was found to be associated with the plasma membrane. These results are discussed in the context of the involvement of the sphingolipids SM and GlcCer in signal transduction pathways in the plasma membrane.

Plakophilin 1 interferes with plakoglobin binding to desmoplakin, yet together with plakoglobin promotes clustering of desmosomal plaque complexes at cell-cell borders

2001 ◽  
Vol 114 (4) ◽  
pp. 727-738 ◽  
Author(s):  
E.A. Bornslaeger ◽  
L.M. Godsel ◽  
C.M. Corcoran ◽  
J.K. Park ◽  
M. Hatzfeld ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Full Length ◽  
Beta Catenin ◽  
Structural Elements ◽  
Lateral Interactions ◽  
Soluble Complex ◽  
Macromolecular Complexes ◽  
Ht1080 Cells ◽  
Associated Proteins ◽  
Filament Networks

Desmosomes are adhesive junctions that link intermediate filament networks to sites of strong intercellular adhesion. These junctions play an important role in providing strength to tissues that experience mechanical stress such as heart and epidermis. The basic structural elements of desmosomes are similar to those of the better-characterized adherens junctions, which anchor actin-containing microfilaments to cadherins at the plasma membrane. This linkage of actin to classic cadherins is thought to occur through an indirect mechanism requiring the associated proteins, alpha- and beta-catenin. In the case of desmosomes, both linear and lateral interactions have been proposed as playing an important role in formation of the plaque and linkage to the cytoskeleton. However, the precise nature of these interactions and how they cooperate in desmosome assembly are poorly understood. Here we employ a reconstitution system to examine the assembly of macromolecular complexes from components found in desmosomes of the differentiated layers of complex tissues. We demonstrate the existence of a Triton-soluble complex of proteins containing full length desmoplakin (DP), the arm protein plakoglobin, and the cytoplasmic domain of the desmosomal cadherin, desmoglein 1 (Dsg1). In addition, full length DP, but not an N-terminal plakoglobin binding domain of DP, co-immunoprecipitated with the Dsg1 tail in the absence of plakoglobin in HT1080 cells. The relative roles of the arm proteins plakoglobin and plakophilin 1 (PKP1) were also investigated. Our results suggest that, in the Triton soluble pool, PKP1 interferes with binding of plakoglobin to full length DP when these proteins are co-expressed. Nevertheless, both plakoglobin and PKP1 are required for the formation of clustered structures containing DP and the Dsg1 tail that ultrastructurally appear similar to desmosomal plaques found in the epidermis. These findings suggest that more than one armadillo family member is required for normal assembly and clustering of the desmosomal plaque in the upper layers of the epidermis.

Sign in / Sign up

Export Citation Format

Share Document