IQGAP1-dysfunction leads to induction of senescence in human vascular smooth muscle cells

Grabowska, Wioleta; Achtabowska, Natalia; Klejman, Agata; Skowronek, Krzysztof; Calka, Malgorzata; Bielak-Żmijewska, Anna

doi:10.1016/j.mad.2020.111295

Cited by 6 publications

(2 citation statements)

References 30 publications

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“…This process might help immune surveillance of senescent cells by natural killer cells [ 183 ]. Furthermore, when the profile of proliferating and senescent human vascular smooth muscle cells are compared, cellular bridge formation and direct transfer occur preferentially in senescent cells [ 184 ]. Again, this indicates that there is an association between TNT formation and the process of aging.…”

Section: Cell–cell Communication Impairment During Agingmentioning

confidence: 99%

Aging Hallmarks and the Role of Oxidative Stress

et al. 2023

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Aging is a complex biological process accompanied by a progressive decline in the physical function of the organism and an increased risk of age-related chronic diseases such as cardiovascular diseases, cancer, and neurodegenerative diseases. Studies have established that there exist nine hallmarks of the aging process, including (i) telomere shortening, (ii) genomic instability, (iii) epigenetic modifications, (iv) mitochondrial dysfunction, (v) loss of proteostasis, (vi) dysregulated nutrient sensing, (vii) stem cell exhaustion, (viii) cellular senescence, and (ix) altered cellular communication. All these alterations have been linked to sustained systemic inflammation, and these mechanisms contribute to the aging process in timing not clearly determined yet. Nevertheless, mitochondrial dysfunction is one of the most important mechanisms contributing to the aging process. Mitochondria is the primary endogenous source of reactive oxygen species (ROS). During the aging process, there is a decline in ATP production and elevated ROS production together with a decline in the antioxidant defense. Elevated ROS levels can cause oxidative stress and severe damage to the cell, organelle membranes, DNA, lipids, and proteins. This damage contributes to the aging phenotype. In this review, we summarize recent advances in the mechanisms of aging with an emphasis on mitochondrial dysfunction and ROS production.

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Section: Cell–cell Communication Impairment During Agingmentioning

confidence: 99%

Aging Hallmarks and the Role of Oxidative Stress

et al. 2023

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“…Logically, both the membrane and the cytoskeleton must play a role in protrusion formation. Indeed, inhibition of actin polymerization abrogates TNT formation and various actin-binding, membrane tethering, signal regulators and actin-regulatory proteins have been implicated in TNT formation and assembly such as Cdc42, IQGAP1, LST1, RalA, M-sec and filamin in various cell types (Hase et al ., 2009; Schiller et al ., 2013; Delage et al ., 2016; Grabowska et al ., 2020; Barutta et al ., 2021; D’Aloia et al ., 2021). Similarly, membrane organization and function are controlled by membrane lipids that sort the membrane into dynamic subdomains, assembling signaling platforms (Takenawa and Itoh, 2001; Wenk, 2005; Simons and Sampaio, 2011; Delage and Zurzolo, 2013).…”

Section: Introductionmentioning

confidence: 99%

CD13 Activation Assembles Signaling Complexes that Promote the Formation of Tunneling Nanotubes in Endothelial Cells

Meredith,

Aguilera,

McGurk

et al. 2024

Preprint

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Transmembrane CD13 assembles protein complexes at the plasma membrane to enable diverse cellular processes such as cell-cell adhesion, focal adhesion turnover, endocytosis and recycling of cell surface proteins. In this study, we demonstrate a novel CD13-dependent assembly platform that regulates phosphoinositide (PI) signal transduction during the formation of Tunneling Nanotubes (TNTs). TNTs are actin-based, membrane-delimited bridges that facilitate intercellular communication by connecting distant cells to physically transfer subcellular cargoes. TNTs form between various cell types under stress conditions, but few molecular TNT-inducers exist. Human Kaposi sarcoma-derived endothelial cells (KSECs) readily form stress-induced TNTs capable of transferring calcium ion and membrane molecules between cells, with clear accumulation of CD13 and actin at the base of the protrusions. Alternatively, CD13-null KSECs form fewer TNTs and calcium ion transfer is markedly reduced. Mechanistically, CD13-mediated TNT formation requires activation of CD13, Src, FAK and Cdc42 to allow tethering of the IQGAP1 and ARF6 complex at the membrane to activate the phosphatidylinositol-4-phosphate-5-kinase PI5K. This increases local phosphatidylinositol 4,5-bisphosphate levels to promote the actin-polymerization and membrane protrusion necessary for TNT formation. Therefore, CD13 is a novel molecular PIP regulator and TNT trigger that will facilitate the dissection of downstream pathways and mechanisms regulating TNT formation.

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