Macropinocytosis: Biology and mechanisms

Kay, Robert R.

doi:10.1016/j.cdev.2021.203713

Cited by 43 publications

(33 citation statements)

References 114 publications

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“…Membrane ruffles can be induced by growth factors (Hoon et al ., 2012; Itoh & Hasegawa, 2013; Kay, 2021; Swanson, 2008). Thus, we analyzed the EGF-stimulated mouse podocyte cell line, MPC5.…”

Section: Resultsmentioning

confidence: 99%

Identification of Circular Dorsal Ruffles as Signal Platforms for the AKT pathways in Glomerular Podocytes

Yoshida

Hua

Torres

et al. 2022

Preprint

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Circular dorsal ruffles (CDRs) are rounded membrane ruffles induced by growth factors to function as precursors of the large-scale endocytosis called macropinocytosis. In cell line systems, CDR/macropinocytosis regulate the AKT-mTORC1 pathway, a canonical growth factor signaling. However, it is not known if this mechanism occurs in tissues. Here, utilizing ultra-high-resolution scanning electron microscopy, we report that CDRs are expressed in glomerular podocytes ex vivo and in vivo. Biochemical and imaging analysis revealed that AKT phosphorylation is localized to CDRs upstream of mTORC1 activation in podocyte cell line and isolated glomeruli, indicating that CDRs function as signal platforms for AKT-mTORC1 pathway in podocytes to maintain the kidney function. Because mTORC1 has critical roles in the podocyte metabolism and the aberrant activation of mTORC1 triggers podocytopathies, these results suggest that targeting CDR formation would be a potential therapeutic approach for the diseases.

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Section: Resultsmentioning

confidence: 99%

Identification of Circular Dorsal Ruffles as Signal Platforms for the AKT pathways in Glomerular Podocytes

Yoshida

Hua

Torres

et al. 2022

Preprint

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“…The process of macropinocytosis includes the interaction of CPP/cargoes and membrane proteoglycans, which activates the rac protein in the cytoplasm. Then, the rac protein releases signals to stimulate the F‐actin organisations, followed by the contraction of actin microfilaments, the deformation, protrusion and endocytosis of cell membrane, and then the cellular uptake of CPPs 34 . Clathrin‐mediated endocytosis, sometimes called as receptor‐mediated endocytosis, is receptor‐guided and clathrin‐mediated endocytosis necessary for the cellular uptake of essential nutrients 35 .…”

Section: The Uptake Mechanism Of Cppsmentioning

confidence: 99%

“…Then, the rac protein releases signals to stimulate the F-actin organisations, followed by the contraction of actin microfilaments, the deformation, protrusion and endocytosis of cell membrane, and then the cellular uptake of CPPs. 34 Clathrin-mediated endocytosis, sometimes called as receptor-mediated endocytosis, is receptor-guided and clathrin-mediated endocytosis necessary for the cellular uptake of essential nutrients. 35 Its mechanism involves the following processes.…”

Section: The Endocytosis-mediated Pathwaymentioning

confidence: 99%

The role of cell‐penetrating peptides in potential anti‐cancer therapy

Zhou

Zou

Cheng

et al. 2022

Clinical & Translational Med

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Due to the complex physiological structure, microenvironment and multiple physiological barriers, traditional anti‐cancer drugs are severely restricted from reaching the tumour site. Cell‐penetrating peptides (CPPs) are typically made up of 5–30 amino acids, and can be utilised as molecular transporters to facilitate the passage of therapeutic drugs across physiological barriers. Up to now, CPPs have widely been used in many anti‐cancer treatment strategies, serving as an excellent potential choice for oncology treatment. However, their drawbacks, such as the lack of cell specificity, short duration of action, poor stability in vivo, compatibility problems (i.e. immunogenicity), poor therapeutic efficacy and formation of unwanted metabolites, have limited their further application in cancer treatment. The cellular uptake mechanisms of CPPs involve mainly endocytosis and direct penetration, but still remain highly controversial in academia. The CPPs‐based drug delivery strategy could be improved by clever design or chemical modifications to develop the next‐generation CPPs with enhanced cell penetration capability, stability and selectivity. In addition, some recent advances in targeted cell penetration that involve CPPs provide some new ideas to optimise CPPs.

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“…Macropinocytosis is an evolutionary conserved non-selective endocytic mechanism that various cell types, from amoeba to mammalian malignant cells and macrophages, use for the uptake of extracellular fluid, including nutrients (e.g., amino acids and glucose), proteins (e.g., albumin and antigens), pathogens and debris (e.g., King and Kay, 2019 ; Palm, 2019 ; Kay, 2021 ). Macropinocytosis, such as phagocytosis, depends on the cytoskeleton, driving the production of plasma membrane ruffles/lamellipodia that first engulf and then internalize extracellular fluid and included cargo (e.g., Mylvaganam et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Galectin-3 (MAC-2) controls phagocytosis and macropinocytosis through intracellular and extracellular mechanisms

Rotshenker

2022

Front. Cell. Neurosci.

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Galectin-3 (Gal-3; formally named MAC-2) is a β-galactoside-binding lectin. Various cell types produce Gal-3 under either normal conditions and/or pathological conditions. Gal-3 can be present in cells' nuclei and cytoplasm, secreted from producing cells, and associated with cells' plasma membranes. This review focuses on how Gal-3 controls phagocytosis and macropinocytosis. Intracellular and extracellular Gal-3 promotes the phagocytosis of phagocytic targets/cargo (e.g., tissue debris and apoptotic cells) in “professional phagocytes” (e.g., microglia and macrophages) and “non-professional phagocytes” (e.g., Schwann cells and astrocytes). Intracellularly, Gal-3 promotes phagocytosis by controlling the “eat me” signaling pathways that phagocytic receptors generate, directing the cytoskeleton to produce the mechanical forces that drive the structural changes on which phagocytosis depends, protrusion and then retraction of filopodia and lamellipodia as they, respectively, engulf and then internalize phagocytic targets. Extracellularly, Gal-3 promotes phagocytosis by functioning as an opsonin, linking phagocytic targets to phagocytic receptors, activating them to generate the “eat me” signaling pathways. Macropinocytosis is a non-selective endocytic mechanism that various cells use to internalize the bulk of extracellular fluid and included materials/cargo (e.g., dissolved nutrients, proteins, and pathogens). Extracellular and intracellular Gal-3 control macropinocytosis in some types of cancer. Phagocytosed and macropinocytosed targets/cargo that reach lysosomes for degradation may rupture lysosomal membranes. Damaged lysosomal membranes undergo either repair or removal by selective autophagy (i.e., lysophagy) that intracellular Gal-3 controls.

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Macropinocytosis: Biology and mechanisms

Cited by 43 publications

References 114 publications

Identification of Circular Dorsal Ruffles as Signal Platforms for the AKT pathways in Glomerular Podocytes

Identification of Circular Dorsal Ruffles as Signal Platforms for the AKT pathways in Glomerular Podocytes

The role of cell‐penetrating peptides in potential anti‐cancer therapy

Galectin-3 (MAC-2) controls phagocytosis and macropinocytosis through intracellular and extracellular mechanisms

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