scholarly journals Cholesterol modulates cell signaling and protein networking by specifically interacting with PDZ domain-containing scaffold proteins

2012 ◽  
Vol 3 (1) ◽  
Author(s):  
Ren Sheng ◽  
Yong Chen ◽  
Heon Yung Gee ◽  
Ewa Stec ◽  
Heather R. Melowic ◽  
...  
Keyword(s):  
Cell Signaling ◽  
Pdz Domain ◽  
Scaffold Proteins

Scaffold Proteins and their Roles in Human Diseases

2020 ◽  
Vol 14 (01) ◽  
pp. 15-29
Author(s):  
Somsubhro Mukherjee ◽  
Boon Chuan Low
Keyword(s):  
Cell Signaling ◽  
Signaling Pathways ◽  
Drug Targets ◽  
Metabolic Diseases ◽  
Scaffold Proteins ◽  
Human Diseases ◽  
Normal Functions ◽  
Cellular Pathways ◽  
Cell Signaling Pathways

Scaffold proteins are critical regulators of important cell signaling pathways. Though scaffolds are not stringently defined in meaning, they are known to interact with numerous components of a signaling pathway, binding and bridging them into distinct and functional complexes. They control signal transduction and assist the localization of pathway components (organized in complexes) to definite regions of the cell such as the endosomes, plasma membrane, the cytoplasm, mitochondria, Golgi, and the nucleus. Years of research in this field have revealed the versatility of this class of protein and the important role it plays in maintaining the normal functions of the human body. Here, we discuss the role of several scaffold proteins which are implicated in important signaling pathways that play important roles in cardiac diseases, metabolic diseases, neurological disorders, and cancer. Their versatility and functions in human diseases make them attractive drug targets, several of which have been investigated in clinical trials. Future studies of scaffold proteins should give us an in-depth knowledge of how cell signaling works in normal and pathological conditions and would offer avenues to disrupt harmful cellular pathways to circumvent diseases.

Organization of Signaling Complexes by PDZ-Domain Scaffold Proteins

ChemInform ◽  
2003 ◽  
Vol 34 (43) ◽  
Author(s):  
Mingjie Zhang ◽  
Wenning Wang
Keyword(s):  
Pdz Domain ◽  
Scaffold Proteins

Mechanism and role of PDZ domains in signaling complex assembly

2001 ◽  
Vol 114 (18) ◽  
pp. 3219-3231 ◽  
Author(s):  
Baruch Z. Harris ◽  
Wendell A. Lim
Keyword(s):  
Cell Signaling ◽  
Pdz Domain ◽  
Photoreceptor Cells ◽  
Protein Recognition ◽  
Pdz Domains ◽  
Peptide Motifs ◽  
Signaling Complex ◽  
Multicellular Organisms ◽  
Drosophila Photoreceptor

PDZ domains are protein-protein recognition modules that play a central role in organizing diverse cell signaling assemblies. These domains specifically recognize short C-terminal peptide motifs, but can also recognize internal sequences that structurally mimic a terminus. PDZ domains can therefore be used in combination to bind an array of target proteins or to oligomerize into branched networks. Several PDZ-domain-containing proteins play an important role in the transport, localization and assembly of supramolecular signaling complexes. Examples of such PDZ-mediated assemblies exist in Drosophila photoreceptor cells and at mammalian synapses. The predominance of PDZ domains in metazoans indicates that this highly specialized scaffolding module probably evolved in response to the increased signaling needs of multicellular organisms.

The Shank family of scaffold proteins

2000 ◽  
Vol 113 (11) ◽  
pp. 1851-1856 ◽  
Author(s):  
M. Sheng ◽  
E. Kim
Keyword(s):  
Pdz Domain ◽  
Scaffold Proteins ◽  
Cell Junctions ◽  
Excitatory Synapses ◽  
Protein Protein Interaction ◽  
Sam Domain ◽  
New Family ◽  
Cytoplasmic Proteins ◽  
Specific Localization ◽  
G Protein Coupled

Shank proteins make up a new family of scaffold proteins recently identified through their interaction with a variety of membrane and cytoplasmic proteins. Shank polypeptides contain multiple sites for protein-protein interaction, including ankyrin repeats, an SH3 domain, a PDZ domain, a long proline-rich region, and a SAM domain. Binding partners for most of these domains have been identified: for instance, the PDZ domain of Shank proteins interacts with GKAP (a postsynaptic-density protein) as well as several G-protein-coupled receptors. The specific localization of Shank proteins at postsynaptic sites of brain excitatory synapses suggests a role for this family of proteins in the organization of cytoskeletal/ signaling complexes at specialized cell junctions.

scholarly journals Membrane Trafficking of Integral Cell Junction Proteins

2021 ◽  
Author(s):  
Arie Horowitz
Keyword(s):  
Membrane Trafficking ◽  
Pdz Domain ◽  
Scaffold Proteins ◽  
Cell Junction ◽  
Current State ◽  
Junction Protein ◽  
Cytoplasmic Tails ◽  
Integral Proteins ◽  
Junction Proteins

Though membrane trafficking of cell junction proteins has been studied extensively for more than two decades, the accumulated knowledge remains fragmentary. The goal of this review is to synthesize the numerous and disparate observations on the membrane trafficking of the five major junction transmembrane proteins accumulated to date to comprehend the current state of the art, to highlight differences and similarities among the trafficking pathways, and to identify topics that are not fully understood. Clathrin-mediated endocytosis appears to be the main but not exclusive mode of internalization. Caveolin-mediated endocytosis and macropinocytosis are employed less frequently. PDZ-domain binding is the predominant mode of interaction between junction protein cytoplasmic tails and scaffold proteins. It is shared by claudins, the largest family of junction integral proteins, and by the three nectins. All five proteins are destined to either recycling via Rab4/Rab11 GTPases or to degradation. The sorting mechanisms that underlie the specificity of their endocytic pathways and determine their fates are not fully known. New data is presented to introduce an emerging role of junction-associated scaffold proteins in claudin membrane trafficking.

Structures and target recognition modes of PDZ domains: recurring themes and emerging pictures

2013 ◽  
Vol 455 (1) ◽  
pp. 1-14 ◽  
Author(s):  
Fei Ye ◽  
Mingjie Zhang
Keyword(s):  
Amino Acid ◽  
Pdz Domain ◽  
Binding Mode ◽  
Structural Features ◽  
Scaffold Proteins ◽  
Amino Acid Residues ◽  
Pdz Domains ◽  
Target Proteins ◽  
Protein Protein Interaction ◽  
Target Binding

PDZ domains are highly abundant protein–protein interaction modules and are often found in multidomain scaffold proteins. PDZ-domain-containing scaffold proteins regulate multiple biological processes, including trafficking and clustering receptors and ion channels at defined membrane regions, organizing and targeting signalling complexes at specific cellular compartments, interfacing cytoskeletal structures with membranes, and maintaining various cellular structures. PDZ domains, each with ~90-amino-acid residues folding into a highly similar structure, are best known to bind to short C-terminal tail peptides of their target proteins. A series of recent studies have revealed that, in addition to the canonical target-binding mode, many PDZ–target interactions involve amino acid residues beyond the regular PDZ domain fold, which we refer to as extensions. Such extension sequences often form an integral structural and functional unit with the attached PDZ domain, which is defined as a PDZ supramodule. Correspondingly, PDZ-domain-binding sequences from target proteins are frequently found to require extension sequences beyond canonical short C-terminal tail peptides. Formation of PDZ supramodules not only affords necessary binding specificities and affinities demanded by physiological functions of PDZ domain targets, but also provides regulatory switches to be built in the PDZ–target interactions. At the 20th anniversary of the discovery of PDZ domain proteins, we try to summarize structural features and target-binding properties of such PDZ supramodules emerging from studies in recent years.

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