Recent work from our laboratory has revealed that isoactin cytoskeletal and membrane dynamics are coordinately regulated. In this chapter, we review some of the recent and relevant scientific literature focusing on key aspects of cytoskeletal and membrane-mediated signal transduction. Additionally, we highlight some of the strategic molecular, biochemical, and cell-based methodologies that we have either developed or implemented in our efforts aimed at revealing the pivotal role(s) that the actin isoforms play in controlling cell shape and motility during developmental and/or disease-associated events. Furthermore, we address the central position of beta-actin and its barbed end-specific capping protein, betacap73, in modulating nonmuscle cell membrane dynamics and cell migration. In studying the molecular mechanisms mediating these cytoskeletal protein interactions, we have recently recognized that cell motility and beta-actin dynamics are controlled by the direct association of betacap73 with the plasma membrane- and endosome-associated protein, ADP-ribosylation factor 6 (Arf6).
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http://dx.doi.org/10.1016/S0076-6879(05)04033-4 | DOI Listing |
Commun Biol
January 2025
Protein Interactome Laboratory for Structural and Functional Biology, Advanced Centre for Treatment, Research and Education in Cancer, Navi Mumbai, India.
Why cancer cells disproportionately accumulate polyubiquitinated proteotoxic proteins despite high proteasomal activity is an outstanding question. While mis-regulated ubiquitination is a contributing factor, here we show that a structurally-perturbed and sub-optimally functioning proteasome is at the core of altered proteostasis in tumors. By integrating the gene coexpression signatures of proteasomal subunits in breast cancer (BrCa) patient tissues with the atomistic details of 26S holocomplex, we find that the transcriptional deregulation induced-stoichiometric imbalances perpetuate with disease severity.
View Article and Find Full Text PDFSci Transl Med
January 2025
College of Pharmaceutical Sciences, State Key Laboratory of Advanced Drug Delivery and Release Systems, Zhejiang University, Hangzhou 310058, China.
Macrophages play a central role in antitumor immunity, making them an attractive target for gene therapy strategies. However, macrophages are difficult to transfect because of nucleic acid sensors that can trigger the degradation of foreign plasmid DNA. Here, we developed a macrophage-specific editing (MAGE) system by which compact plasmid DNA encoding a CasRx editor can be delivered to macrophages by a poly(β-amino ester) (PBAE) carrier to bypass the DNA sensor and enable RNA editing in vitro and in vivo.
View Article and Find Full Text PDFiScience
January 2025
Laboratory of Antibody Discovery and Accelerated Protein Therapeutics, Center for Infectious Diseases, Houston Methodist Research Institute and Department of Pathology and Genomic Medicine, Houston Methodist Hospital, Houston, TX, USA.
T7 RNA polymerase (RNAP) has enabled orthogonal control of gene expression and recombinant protein production across diverse prokaryotic host chassis organisms for decades. However, the absence of 5' methyl guanosine caps on T7 RNAP-derived transcripts has severely limited its utility and widespread adoption in eukaryotic systems. To address this shortcoming, we evolved a fusion enzyme combining T7 RNAP with the single subunit capping enzyme from African swine fever virus using .
View Article and Find Full Text PDFJ Biol Chem
January 2025
Departamento de Bioquímica, IQ, Universidade de São Paulo, 05508-000, São Paulo, Brazil.
The Min system is a key spatial regulator of cell division in rod-shaped bacteria and the first FtsZ negative modulator to be recognized. Nevertheless, despite extensive genetic and in vitro studies, the molecular mechanism used by MinC to inhibit Z-ring formation remains incompletely understood. The crystallization of FtsZ in complex with other negative regulators such as SulA and MciZ has provided important structural information to corroborate in vitro experiments and establish the mechanism of Z-ring antagonism by these modulators.
View Article and Find Full Text PDFJ Vector Borne Dis
January 2025
Department of Zoology, Faculty of Science, University of Jaffna, Jaffna, Sri Lanka.
Background And Objectives: Salivary glands proteins but not glycoconjugates have been previously studied in mosquito vectors of human diseases. Glycoconjugates from salivary gland-derived proteins from human-feeding tick vectors can elicit hypersensitivity reactions which may also occur with mosquito bites. Protein glycoconjugate in salivary glands of the principal arboviral vector Aedes aegypti and the rapidly spreading malaria vector Anopheles stephensi were therefore investigated.
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