Scaffold Proteins in Health, Disease, and Therapy

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (31 August 2022) | Viewed by 9209

Special Issue Editors

Departament of Biochemistry, Microbiology, Cell Biology and Genetics, University of La Laguna, Av Astrofisico Fco Sanchez s/n, 38206 La Laguna, Tenerife, Spain
Interests: stem cells; gene expression; regeneration; cancer research; cancer stem cells; stem cell differentiation; tumor angiogenesis; tumor stem cells; neural development, tumor microenvironment, glioblastoma, colorectal cancer; Na,K‐ATPase
Special Issues, Collections and Topics in MDPI journals
1. Department of Physiology, School of Medicine, Complutense University of Madrid, Madrid, Spain
2. Renal Physiopathology Laboratory, Gregorio Marañón Health Research Institute (IiSGM), Hospital General Universitario Gregorio Marañón, 28007 Madrid, Spain
Interests: acute kidney injury; chronic kidney disease; nephrotoxicity; nephroprotection; cisplatin; sepsis; rhabdomyolysis; malaria-induced kidney damage; apoptosis; oxidative stress; inflammation; fibrosis

Special Issue Information

Dear Colleagues,

Scaffold proteins, scaffoldins, scaffolins, or scaffolding proteins are a growing group of proteins involved in signaling paths regulating cell fate, morphogenesis and polarity, migration, tumor-cell biology, and many more cellular functions and molecular architecture. Some of them vary in terms of expression levels, localization, function, and structure in disease, in tissue repair, and with therapy.

Proteins belonging to the scaffoldin growing group share four common functional properties: they 1) physically cluster all proteins involved in a functional node, 2) locate the node in discrete subcellular compartments, 3) coordinate positive and negative stimuli to the node, and 4) encase and protect all proteins in the node from inactivation and/or degradation originating outside the pathway.

In this Special Issue, we propose to publish original research articles and reviews from researchers and laboratories working in expression, structure, and function of scaffold proteins in health, disease, and therapy.

Prof. Dr. Pablo Martín-Vasallo
Dr. Alberto Lazaro
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (4 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Research

Jump to: Review

13 pages, 2606 KiB  
Article
The Scaffold Immunophilin FKBP51 Is a Phosphoprotein That Undergoes Dynamic Mitochondrial-Nuclear Shuttling
by Nadia R. Zgajnar, Cristina Daneri-Becerra, Ana Cauerhff and Mario D. Galigniana
Cells 2022, 11(23), 3771; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11233771 - 25 Nov 2022
Cited by 4 | Viewed by 1239
Abstract
The immunophilin FKBP51 forms heterocomplexes with molecular chaperones, protein-kinases, protein-phosphatases, autophagy-related factors, and transcription factors. Like most scaffold proteins, FKBP51 can use a simple tethering mechanism to favor the efficiency of interactions with partner molecules, but it can also exert more complex allosteric [...] Read more.
The immunophilin FKBP51 forms heterocomplexes with molecular chaperones, protein-kinases, protein-phosphatases, autophagy-related factors, and transcription factors. Like most scaffold proteins, FKBP51 can use a simple tethering mechanism to favor the efficiency of interactions with partner molecules, but it can also exert more complex allosteric controls over client factors, the immunophilin itself being a putative regulation target. One of the simplest strategies for regulating pathways and subcellular localization of proteins is phosphorylation. In this study, it is shown that scaffold immunophilin FKBP51 is resolved by resolutive electrophoresis in various phosphorylated isoforms. This was evidenced by their reactivity with specific anti-phosphoamino acid antibodies and their fade-out by treatment with alkaline phosphatase. Interestingly, stress situations such as exposure to oxidants or in vivo fasting favors FKBP51 translocation from mitochondria to the nucleus. While fasting involves phosphothreonine residues, oxidative stress involves tyrosine residues. Molecular modeling predicts the existence of potential targets located at the FK1 domain of the immunophilin. Thus, oxidative stress favors FKBP51 dephosphorylation and protein degradation by the proteasome, whereas FK506 binding protects the persistence of the post-translational modification in tyrosine, leading to FKBP51 stability under oxidative conditions. Therefore, FKBP51 is revealed as a phosphoprotein that undergoes differential phosphorylations according to the stimulus. Full article
(This article belongs to the Special Issue Scaffold Proteins in Health, Disease, and Therapy)
Show Figures

Figure 1

18 pages, 8330 KiB  
Article
FKBP51, AmotL2 and IQGAP1 Involvement in Cilastatin Prevention of Cisplatin-Induced Tubular Nephrotoxicity in Rats
by Rebeca González-Fernández, María Ángeles González-Nicolás, Manuel Morales, Julio Ávila, Alberto Lázaro and Pablo Martín-Vasallo
Cells 2022, 11(9), 1585; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11091585 - 09 May 2022
Cited by 2 | Viewed by 2224
Abstract
The immunophilin FKBP51, the angiomotin AmotL2, and the scaffoldin IQGAP1 are overexpressed in many types of cancer, with the highest increase in leucocytes from patients undergoing oxaliplatin chemotherapy. Inflammation is involved in the pathogenesis of nephrotoxicity induced by platinum analogs. Cilastatin prevents renal [...] Read more.
The immunophilin FKBP51, the angiomotin AmotL2, and the scaffoldin IQGAP1 are overexpressed in many types of cancer, with the highest increase in leucocytes from patients undergoing oxaliplatin chemotherapy. Inflammation is involved in the pathogenesis of nephrotoxicity induced by platinum analogs. Cilastatin prevents renal damage caused by cisplatin. This functional and confocal microscopy study shows the renal focal-segmental expression of TNFα after cisplatin administration in rats, predominantly of tubular localization and mostly prevented by co-administration of cilastatin. FKBP51, AmotL2 and IQGAP1 protein expression increases slightly with cilastatin administration and to a much higher extent with cisplatin, in a cellular- and subcellular-specific manner. Kidney tubule cells expressing FKBP51 show either very low or no expression of TNFα, while cells expressing TNFα have low levels of FKBP51. AmotL2 and TNFα seem to colocalize and their expression is increased in tubular cells. IQGAP1 fluorescence increases with cilastatin, cisplatin and joint cilastatin-cisplatin treatment, and does not correlate with TNFα expression or localization. These data suggest a role for FKBP51, AmotL2 and IQGAP1 in cisplatin toxicity in kidney tubules and in the protective effect of cilastatin through inhibition of dehydropeptidase-I. Full article
(This article belongs to the Special Issue Scaffold Proteins in Health, Disease, and Therapy)
Show Figures

Figure 1

24 pages, 4935 KiB  
Article
A-Kinase Anchoring Protein 2 Promotes Protection against Myocardial Infarction
by Darko Maric, Aleksandra Paterek, Marion Delaunay, Irene Pérez López, Miroslav Arambasic and Dario Diviani
Cells 2021, 10(11), 2861; https://0-doi-org.brum.beds.ac.uk/10.3390/cells10112861 - 23 Oct 2021
Cited by 7 | Viewed by 2994
Abstract
Myocardial infarction (MI) is a leading cause of maladaptive cardiac remodeling and heart failure. In the damaged heart, loss of function is mainly due to cardiomyocyte death and remodeling of the cardiac tissue. The current study shows that A-kinase anchoring protein 2 (AKAP2) [...] Read more.
Myocardial infarction (MI) is a leading cause of maladaptive cardiac remodeling and heart failure. In the damaged heart, loss of function is mainly due to cardiomyocyte death and remodeling of the cardiac tissue. The current study shows that A-kinase anchoring protein 2 (AKAP2) orchestrates cellular processes favoring cardioprotection in infarcted hearts. Induction of AKAP2 knockout (KO) in cardiomyocytes of adult mice increases infarct size and exacerbates cardiac dysfunction after MI, as visualized by increased left ventricular dilation and reduced fractional shortening and ejection fraction. In cardiomyocytes, AKAP2 forms a signaling complex with PKA and the steroid receptor co-activator 3 (Src3). Upon activation of cAMP signaling, the AKAP2/PKA/Src3 complex favors PKA-mediated phosphorylation and activation of estrogen receptor α (ERα). This results in the upregulation of ER-dependent genes involved in protection against apoptosis and angiogenesis, including Bcl2 and the vascular endothelial growth factor a (VEGFa). In line with these findings, cardiomyocyte-specific AKAP2 KO reduces Bcl2 and VEGFa expression, increases myocardial apoptosis and impairs the formation of new blood vessels in infarcted hearts. Collectively, our findings suggest that AKAP2 organizes a transcriptional complex that mediates pro-angiogenic and anti-apoptotic responses that protect infarcted hearts. Full article
(This article belongs to the Special Issue Scaffold Proteins in Health, Disease, and Therapy)
Show Figures

Figure 1

Review

Jump to: Research

27 pages, 1921 KiB  
Review
SAPAP Scaffold Proteins: From Synaptic Function to Neuropsychiatric Disorders
by Yunxia Bai, Huimin Wang and Chunxia Li
Cells 2022, 11(23), 3815; https://0-doi-org.brum.beds.ac.uk/10.3390/cells11233815 - 28 Nov 2022
Cited by 5 | Viewed by 1948
Abstract
Excitatory (glutamatergic) synaptic transmission underlies many aspects of brain activity and the genesis of normal human behavior. The postsynaptic scaffolding proteins SAP90/PSD-95-associated proteins (SAPAPs), which are abundant components of the postsynaptic density (PSD) at excitatory synapses, play critical roles in synaptic structure, formation, [...] Read more.
Excitatory (glutamatergic) synaptic transmission underlies many aspects of brain activity and the genesis of normal human behavior. The postsynaptic scaffolding proteins SAP90/PSD-95-associated proteins (SAPAPs), which are abundant components of the postsynaptic density (PSD) at excitatory synapses, play critical roles in synaptic structure, formation, development, plasticity, and signaling. The convergence of human genetic data with recent in vitro and in vivo animal model data indicates that mutations in the genes encoding SAPAP1–4 are associated with neurological and psychiatric disorders, and that dysfunction of SAPAP scaffolding proteins may contribute to the pathogenesis of various neuropsychiatric disorders, such as schizophrenia, autism spectrum disorders, obsessive compulsive disorders, Alzheimer’s disease, and bipolar disorder. Here, we review recent major genetic, epigenetic, molecular, behavioral, electrophysiological, and circuitry studies that have advanced our knowledge by clarifying the roles of SAPAP proteins at the synapses, providing new insights into the mechanistic links to neurodevelopmental and neuropsychiatric disorders. Full article
(This article belongs to the Special Issue Scaffold Proteins in Health, Disease, and Therapy)
Show Figures

Figure 1

Back to TopTop