The field of phosphoinositide signaling has expanded significantly in recent years. Phosphoinositides (also known as phosphatidylinositol phosphates or PIPs) are universal signaling molecules that directly interact with membrane proteins or with cytosolic proteins containing domains that directly bind phosphoinositides and are recruited to cell membranes. Through the activities of phosphoinositide kinases and phosphoinositide phosphatases, seven distinct phosphoinositide lipid molecules are formed from the parent molecule, phosphatidylinositol. PIP signals regulate a wide range of cellular functions, including cytoskeletal assembly, membrane budding and fusion, ciliogenesis, vesicular transport, and signal transduction. Given the many excellent reviews on phosphoinositide kinases, phosphoinositide phosphatases, and PIPs in general, in this review, we discuss recent studies and advances in PIP lipid signaling in the retina. We specifically focus on PIP lipids from vertebrate (e.g., bovine, rat, mouse, toad, and zebrafish) and invertebrate (e.g., Drosophila, horseshoe crab, and squid) retinas. We also discuss the importance of PIPs revealed from animal models and human diseases, and methods to study PIP levels both in vitro and in vivo. We propose that future studies should investigate the function and mechanism of activation of PIP-modifying enzymes/phosphatases and further unravel PIP regulation and function in the different cell types of the retina.
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http://dx.doi.org/10.1194/jlr.TR120000806 | DOI Listing |
J Immunol
February 2025
Department of Immunology, Tufts University School of Medicine, Boston, MA, United States.
The life cycle of effector T cells is determined by signals downstream of the T cell receptor (TCR) that induce activation and proinflammatory activity, or death as part of the process to resolve inflammation. We recently reported that T cell myeloid differentiation primary response 88 (MyD88) tunes down TCR activation and limits T cell survival in the cardiac and tumor inflammatory environments, in contrast to its proinflammatory role in myeloid cells upon toll-like receptor (TLR) recognition of pathogen- and damage-associated molecular patterns. However, the molecular mechanism remains unknown.
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March 2025
Institute of Clinical Biochemistry, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625, Hannover, Germany.
Interleukin-6 (IL-6) is a multifunctional cytokine with important functions in health and disease. In order to activate its target cells, IL-6 binds first to the IL-6 receptor (IL-6R), which in turn induces the recruitment and homodimerization of the signal-transducing β-receptor gp130 and the activation of intracellular signaling cascades, including the phosphoinositide 3-kinase (PI3K)-AKT cascade. IL-6 is involved in the pathogenesis of multiple inflammatory diseases, and tocilizumab, a monoclonal antibody that binds to the IL-6R and thus blocks the biological activities of IL-6, is in clinical use worldwide for the treatment of patients with inflammatory diseases, including rheumatoid arthritis.
View Article and Find Full Text PDFBiologics
March 2025
Key Laboratory of Dunhuang Medicine and Transformation, Ministry of Education, Gansu, People's Republic of China.
Bronchial asthma is a complex and heterogeneous disease with ongoing airway inflammation and increased airway responsiveness. Key characteristics of the disease include persistent airway inflammation, airway hyperresponsiveness, and airway remodeling. Asthma's chronic and recurrent characteristics contribute to airway remodeling and inflammation, which can exacerbate lung damage.
View Article and Find Full Text PDFElife
March 2025
Department of Physiology and Biophysics, Stony Brook University, Stony Brook, New York, United States.
Most human pancreatic ductal adenocarcinoma (PDAC) are not infiltrated with cytotoxic T cells and are highly resistant to immunotherapy. Over 90% of PDAC have oncogenic KRAS mutations, and phosphoinositide 3-kinases (PI3Ks) are direct effectors of KRAS. Our previous study demonstrated that ablation of in KPC (; ; ) pancreatic cancer cells induced host T cells to infiltrate and completely eliminate the tumors in a syngeneic orthotopic implantation mouse model.
View Article and Find Full Text PDFSheng Li Xue Bao
February 2025
Center for Translation Medicine Research on Sensory-Motor Diseases, Yan'an University, Yan'an 716000, China.
Endothelin-1 is a peptide derived from endothelial cells, consisting of 21 amino acid residues. In recent years, research has found that endothelin-1 not only plays a key role in vascular tone regulation but also participates in the occurrence and development of various types of pathological pain, including inflammatory pain, neuropathic pain, and cancer pain. Endothelin-1 binds to its receptors and activates multiple signaling pathways such as protein kinase C, calcium ion channels, and the phosphoinositide pathway, thereby influencing neuronal excitability and nociceptive information transmission.
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