Commisso C. (ed.) Macropinocytosis: Functions and Mechanisms

New York: Springer, 2022. — 227 p.This book presents the functions and mechanisms of macropinocytosis, an actin-driven endocytic uptake process.
Key points, including the evolutionary origins of macropinocytosis and major signaling pathways that regulate this uptake mechanism, are highlighted. A wide-array of functions of macropinocytosis are described, including cellular metabolism, cell death, cell migration and antigen presentation. Macropinocytosis has recently been recognized as a critical pathway in disease pathology and treatment. Therefore, a broad overview of macropinocytosis will benefit clinicians, as well as translational and basic research scientists. Moreover, as one of the main clathrin-independent endocytic routes, compiling all the critical information about macropinocytosis in one collection, this book will also be helpful to educators and their students.Macropinocytosis: Functions and Mechanisms
Macropinocytosis: A Diverse Landscape of Functionality
Regulation of Macropinocytosis by Signaling MoleculesAbout the Editor
Functions of Macropinocytosis
Functional Diversity of MacropinocytosisNutrient Transporters: A Specialized Protein Pumps to Intake Small Molecules
``Endocytosis´´: Intake of Macromolecules
Phagocytosis
Pinocytosis
Clathrin-Mediated Endocytosis
Caveolae-Mediated Endocytosis
Macropinocytosis
Functions of Macropinocytosis in Different Cell Types
Role in Immune Surveillance
Role in Fueling Cancer Cells
Role in Inducing Methuosis
ConclusionsMacropinocytosis and Cancer: From Tumor Stress to Signaling PathwaysNutrient Deprivation as a Driver of Macropinocytosis
Amino Acid Scarcity and Macropinocytosis
Macropinocytosis in the Setting of Glucose Deprivation
Macropinocytosis and Oxidative Stress
Macropinocytosis and Hypoxia
Signaling Pathways That Regulate Macropinocytosis in the Context of Tumor Stress
Growth Factors and Cytokines
Ras, Rac, and PI3K
mTOR
PTEN and AMPK
Concluding RemarksThe Amoebal Model for MacropinocytosisThe Dictyostelium Model for Macropinocytosis
PIP3 Domains and Macropinocytosis
How Macropinosomes Form
Genetics of Macropinocytosis
Cytoskeletal Proteins and the Structure of Macropinocytic Cups
Signalling Proteins and the PIP3 Domain
Shaping Macropinocytic Cups: PIP3 Domains and SCAR/WAVE Rings
Conclusions and Future PerspectivesExtracellular ATP and Macropinocytosis: Their Interactive and Mutually Supportive Roles in Cell Growth, Drug Resist...Intratumoral Extracellular ATP
Macropinocytosis
Scientific and Technological Challenges in ATP Research
Instability of ATP
ATP Release from Macropinosomes
Multi-locational and Multi-functional Extracellular ATP in Cancer
ATP as an Energy Provider for Biochemical Reactions
ATP as a Phosphate Donor for Protein Phosphorylation and Signal Transduction
Beyond Drug Resistance: eATP Induces EMT
ATP and TGF-β
Macropinocytosis as a Self-Propelled Process in Cancer Cells
Targeting Macropinocytosis and eATP in Cancer Therapy
Targeting Macropinocytosis
Targeting Extracellular ATP
Conclusions and Future Research PerspectivesMacropinocytosis and Cell Migration: Don´t Drink and Drive
Macropinocytosis Versus Cell Migration: Two Antagonistic Processes
Antagonism Between Macropinocytosis and Cell Migration: Molecular Mechanisms
The Role of Small GTPases
The Role of Phosphoinositides
Compartmentalization of the Actomyosin Cytoskeleton
Physiological Impact of the Antagonism Between Macropinocytosis and Cell Migration
Environment Exploration
Cell Guidance by Extracellular CuesMacropinocytosis in Phagocyte Function and ImmunityConstitutive Macropinocytosis: Turning Ruffles in Vesicles
Constitutive Macropinocytosis in Pathogen and Damage Sensing
Constitutive Macropinocytosis and Antigen Presentation
Emerging Roles for Macropinocytosis in Phagocyte FunctionSignaling Mechanisms Driving Macropinocytosis
Roles for 3´ Phosphoinositides in MacropinocytosisPhosphoinositides and the Enzymes that Affect their Abundance
Enzymes that Synthesize or Degrade 3´PIs
How Phosphoinositides Organize Cytoplasm
Localization and Mapping of 3´PIs and Associated Chemistries
The Cellular Activities Essential for Macropinocytosis
3´PI-Dependent Activities of Macropinocytosis
Class I PI3K Is Necessary for Some But not all Ruffling
Class I PI3K and Macropinosome Closure
PtdIns3P Facilitates Macropinosome Formation and Macropinosome Maturation
Synthesis of PtdIns(3,5)P2 by PIKfyve Mediates Macropinosome Shrinkage
Roles for PI3K in Macropinocytosis by Dictyostelium discoideum
Feedback Regulation of Macropinocytosis by 3´PIs
Remaining QuestionsSignaling Pathways that Regulate Macropinocytosis in Mammalian CellsCell-Intrinsic Signaling Events that Regulate Macropinosome Formation
The Process of Macropinocytosis
Ras and PI3-Kinase: The Central Regulators of Macropinocytosis
Downstream Effectors of Ras and PI3-Kinase
Intracellular Fate of Macropinosomes
Regulation of Macropinocytosis by Growth Factor Signaling
Cell-Extrinsic Regulation of Macropinocytosis by Growth Factors
Transduction of Growth Factor Signals by Receptor Tyrosine Kinases
Receptor Tyrosine Kinase Signaling Through the Ras and PI3-Kinase Pathways
Metabolic Regulation of Macropinocytosis
Coordination of Cellular Functions with Metabolic Environment Through Nutrient Sensors
Regulation of Macropinocytosis by AMPK
Regulation of Macropinocytic Cargo Degradation by mTORC1
Regulation of mTORC1 by Macropinocytosis
Similarities and Differences between Macropinocytosis and Autophagy
Induction of Macropinocytosis by Signaling Pathways that Regulate Development and Tissue Homeostasis
Transcriptional Macropinocytosis Regulation by Hippo Signaling
Transcriptional and Acute Macropinocytosis Regulation by Canonical Wnt Signaling
Regulation of Macropinocytosis by Oncogenic Signaling
Concluding RemarksWnt, GSK3, and MacropinocytosisEndosomal Sequestration of GSK3 during Wnt Signaling
Macropinocytosis
RTK Growth Factor Signaling and Macropinocytosis
Canonical Wnt and Macropinocytosis
Macropinocytosis is Induced by Loss-of-Function of APC and Axin1
Rapid Macropinocytosis Induction by Wnt in the Absence of New Protein Synthesis
GSK3 Represses Macropinocytosis
Endocytosis and Canonical Wnt Signaling
Wnt-induced Macropinocytosis Increases Lysosomal Acidification and Activity
ConclusionsKRAS Addiction Promotes Cancer Cell Adaptation in Harsh Microenvironment Through Macropinocytosis
KRAS Addiction in Cancer
KRAS, a Multifaceted Protein
KRAS-driven Cancer Heterogeneity, a Hint to Understand KRAS Addiction
KRAS Localization, a Critical Aspect of KRAS Addiction
Tumor Microenvironment, a Clandestine Modulator of KRAS Addiction
Macropinocytosis and Cancer Cell Adaptation
Macropinocytosis, an Advantage for KRAS-Addicted Cell Promoting Survival
Integrin, a Key Mediator of KRAS-Driven Macropinocytosis
Integrin Trafficking, a Modulator of Cell MetabolismKRASG12R-Independent Macropinocytosis in Pancreatic CancerKRAS-Dependent Constitutive Macropinocytosis in Pancreatic Cancer
The Atypical KRASG12R Mutant Has Disrupted Regulator Interactions
KRASG12R Cannot Bind to p110α and Fails to Promote Macropinocytosis
The (Non)redundant Role of PI3K Isoforms in KRASG12R Macropinocytosis
Tying it all Together