Actin-related protein 2/3 complex plays a critical role in the aquaporin-2 exocytotic pathway

Liu, Chen-Chung Steven; Cheung, Pui W.; Dinesh, Anupama; Baylor, Noah; Paunescu, Theodor C.; Nair, Anil V.; Bouley, Richard; Brown, Dennis

doi:10.1152/ajprenal.00015.2021

Cited by 9 publications

(4 citation statements)

References 85 publications

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“…Cellular responses to these external cues are regulated intracellularly through numerous signaling cascades, which include the Rho family of small GTPases and their downstream protein kinase effectors. Arp2/3 complex is a key factor in actin filament branching and polymerization, essential for dendritic spine structural plasticity and stability (54) which was upregulated in LSD exposed organoids. LSD also modulated Rho GTPase CDC42, the protein kinase PAK1, and WASF1, a member of the actin regulatory WAVE complex.…”

Section: Resultsmentioning

confidence: 99%

LSD Modulates Proteins Involved in Cell Proteostasis, Energy Metabolism and Neuroplasticity in Human Cerebral Organoids

Costa,

Goto-Silva,

Nascimento

et al. 2024

Preprint

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The effects of psychedelics encompass modulation of subjective experience, neuronal plasticity, brain activity and connectivity, constituting a complex phenomenon. Underlying these effects, molecular changes at the protein level are expected. Proteomic analysis of human brain cells can elicit a comprehensive view of proteins and biological processes regulated within the central nervous system. To explore the molecular pathways influenced by lysergic acid diethylamide (LSD), we utilized mass spectrometry-based proteomics on human brain organoids. This approach allowed for an in-depth analysis of the proteomic alterations induced by LSD, providing insights into its effects at the molecular level within a brain-like environment. Alterations in proteostasis and energy metabolism, which are required for neural plasticity, were observed. Alongside, we identified changes in protein synthesis, folding, autophagy, and proteasomal degradation, as well as in glycolysis, oxidative phosphorylation, cytoskeleton regulation, and neurotransmitter release, providing a comprehensive view of the regulation of cellular process by LSD exposure. Furthermore, the ability of LSD to induce plasticity in human brain cells was corroborated through complementaryin vitroexperiments focusing on neurite outgrowth. This study sheds light on the specific proteins that LSD influences, thereby enhancing neurite extension and plasticity.

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Section: Resultsmentioning

confidence: 99%

LSD Modulates Proteins Involved in Cell Proteostasis, Energy Metabolism and Neuroplasticity in Human Cerebral Organoids

Costa,

Goto-Silva,

Nascimento

et al. 2024

Preprint

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“…The actin-related protein (Arp)2/3 complex is a key factor in actin filament branching and polymerization. Inhibition of the Arp2/3 complex has been shown to prevent AQP2 exocytosis [ 52 ]. Using 3D super-resolution microscopy, Holst et al reported that association of AQP2-containing vesicles with F-actin is enhanced by serine 256 phosphorylation [ 53 ].…”

Section: The Role Of the Cytoskeleton In Aqp2 Traffickingmentioning

confidence: 99%

Updates and Perspectives on Aquaporin-2 and Water Balance Disorders

Noda

Sasaki

2021

IJMS

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Ensuring the proper amount of water inside the body is essential for survival. One of the key factors in the maintenance of body water balance is water reabsorption in the collecting ducts of the kidney, a process that is regulated by aquaporin-2 (AQP2). AQP2 is a channel that is exclusively selective for water molecules and impermeable to ions or other small molecules. Impairments of AQP2 result in various water balance disorders, including nephrogenic diabetes insipidus (NDI), which is a disease characterized by a massive loss of water through the kidney and consequent severe dehydration. Dysregulation of AQP2 is also a cause of water retention with hyponatremia in heart failure, hepatic cirrhosis, and syndrome of inappropriate antidiuretic hormone secretion (SIADH). Antidiuretic hormone vasopressin is an upstream regulator of AQP2. Its binding to the vasopressin V2 receptor promotes AQP2 targeting to the apical membrane and thus enables water reabsorption. Tolvaptan, a vasopressin V2 receptor antagonist, is effective and widely used for water retention with hyponatremia. However, there are no studies showing improvement in hard outcomes or long-term prognosis. A possible reason is that vasopressin receptors have many downstream effects other than AQP2 function. It is expected that the development of drugs that directly target AQP2 may result in increased treatment specificity and effectiveness for water balance disorders. This review summarizes recent progress in studies of AQP2 and drug development challenges for water balance disorders.

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“…Together, these data suggest that phosphorlyation of AQP2 alters local actin dynamics by altering the concentrations of G-actin and TM5b, in order to locally disrupt the cortical actin network and provide a path to the membrane for AQP2-bearing vesicles. Recently it has been suggested that the Arp2/3 complex, which generates nucleation sites for actin filament branching, is required for AQP2 exit from the trans-Golgi network [64] , [65] , but the mechanism is not yet understood.…”

Section: Introductionmentioning

confidence: 99%