scholarly journals Review of PIP2 in Cellular Signaling, Functions and Diseases

2020 ◽  
Vol 21 (21) ◽  
pp. 8342
Author(s):  
Kalpana Mandal
Keyword(s):  
Molecular Mechanisms ◽  
Membrane Dynamics ◽  
Actin Dynamics ◽  
Cellular Functions ◽  
Phosphatidylinositol Bisphosphate ◽  
Cell Matrix ◽  
Intracellular Proteins ◽  
Specific Proteins ◽  
Cellular Compartments ◽  
Cell Matrix Adhesion

Phosphoinositides play a crucial role in regulating many cellular functions, such as actin dynamics, signaling, intracellular trafficking, membrane dynamics, and cell–matrix adhesion. Central to this process is phosphatidylinositol bisphosphate (PIP2). The levels of PIP2 in the membrane are rapidly altered by the activity of phosphoinositide-directed kinases and phosphatases, and it binds to dozens of different intracellular proteins. Despite the vast literature dedicated to understanding the regulation of PIP2 in cells over past 30 years, much remains to be learned about its cellular functions. In this review, we focus on past and recent exciting results on different molecular mechanisms that regulate cellular functions by binding of specific proteins to PIP2 or by stabilizing phosphoinositide pools in different cellular compartments. Moreover, this review summarizes recent findings that implicate dysregulation of PIP2 in many diseases

scholarly journals Actin Dynamics Associated with Focal Adhesions

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Corina Ciobanasu ◽  
Bruno Faivre ◽  
Christophe Le Clainche
Keyword(s):  
Extracellular Matrix ◽  
Molecular Mechanisms ◽  
Body Force ◽  
Focal Adhesions ◽  
Stress Fibers ◽  
Actin Dynamics ◽  
Actin Assembly ◽  
Force Transmission ◽  
Cell Matrix ◽  
Cell Matrix Adhesion

Cell-matrix adhesion plays a major role during cell migration. Proteins from adhesion structures connect the extracellular matrix to the actin cytoskeleton, allowing the growing actin network to push the plasma membrane and the contractile cables (stress fibers) to pull the cell body. Force transmission to the extracellular matrix depends on several parameters including the regulation of actin dynamics in adhesion structures, the contractility of stress fibers, and the mechanosensitive response of adhesion structures. Here we highlight recent findings on the molecular mechanisms by which actin assembly is regulated in adhesion structures and the molecular basis of the mechanosensitivity of focal adhesions.

scholarly journals Arg interacts with cortactin to promote adhesion-dependent cell edge protrusion

2009 ◽  
Vol 185 (3) ◽  
pp. 503-519 ◽  
Author(s):  
Stefanie Lapetina ◽  
Christopher C. Mader ◽  
Kazuya Machida ◽  
Bruce J. Mayer ◽  
Anthony J. Koleske
Keyword(s):  
Actin Polymerization ◽  
Molecular Mechanisms ◽  
Sh2 Domain ◽  
Cell Edge ◽  
Cell Matrix ◽  
C Terminus ◽  
Dependent Cell ◽  
Src Homology ◽  
Fibroblast Adhesion ◽  
Cell Matrix Adhesion

The molecular mechanisms by which the Abelson (Abl) or Abl-related gene (Arg) kinases interface with the actin polymerization machinery to promote cell edge protrusions during cell–matrix adhesion are unclear. In this study, we show that interactions between Arg and the Arp2/3 complex regulator cortactin are essential to mediate actin-based cell edge protrusion during fibroblast adhesion to fibronectin. Arg-deficient and cortactin knockdown fibroblasts exhibit similar defects in adhesion-dependent cell edge protrusion, which can be restored via reexpression of Arg and cortactin. Arg interacts with cortactin via both binding and catalytic events. The cortactin Src homology (SH) 3 domain binds to a Pro-rich motif in the Arg C terminus. Arg mediates adhesion-dependent phosphorylation of cortactin, creating an additional binding site for the Arg SH2 domain. Mutation of residues that mediate Arg–cortactin interactions abrogate the abilities of both proteins to support protrusions, and the Nck adapter, which binds phosphocortactin, is also required. These results demonstrate that interactions between Arg, cortactin, and Nck1 are critical to promote adhesion-dependent cell edge protrusions.

scholarly journals Plexin-B2 orchestrates collective stem cell dynamics via actomyosin contractility, cytoskeletal tension and adhesion

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Chrystian Junqueira Alves ◽  
Rafael Dariolli ◽  
Jonathan Haydak ◽  
Sangjo Kang ◽  
Theodore Hannah ◽  
...  
Keyword(s):  
Stem Cells ◽  
Stem Cell ◽  
Molecular Mechanisms ◽  
Cell Physiology ◽  
Matrix Adhesion ◽  
Cell Matrix ◽  
Actomyosin Contractility ◽  
Cytoskeletal Tension ◽  
Cell Matrix Adhesion ◽  
Cell Cell

AbstractDuring morphogenesis, molecular mechanisms that orchestrate biomechanical dynamics across cells remain unclear. Here, we show a role of guidance receptor Plexin-B2 in organizing actomyosin network and adhesion complexes during multicellular development of human embryonic stem cells and neuroprogenitor cells. Plexin-B2 manipulations affect actomyosin contractility, leading to changes in cell stiffness and cytoskeletal tension, as well as cell-cell and cell-matrix adhesion. We have delineated the functional domains of Plexin-B2, RAP1/2 effectors, and the signaling association with ERK1/2, calcium activation, and YAP mechanosensor, thus providing a mechanistic link between Plexin-B2-mediated cytoskeletal tension and stem cell physiology. Plexin-B2-deficient stem cells exhibit premature lineage commitment, and a balanced level of Plexin-B2 activity is critical for maintaining cytoarchitectural integrity of the developing neuroepithelium, as modeled in cerebral organoids. Our studies thus establish a significant function of Plexin-B2 in orchestrating cytoskeletal tension and cell-cell/cell-matrix adhesion, therefore solidifying the importance of collective cell mechanics in governing stem cell physiology and tissue morphogenesis.

scholarly journals Kindlins in FERM adhesion

Blood ◽  
2010 ◽  
Vol 115 (20) ◽  
pp. 4011-4017 ◽  
Author(s):  
Nikolay L. Malinin ◽  
Edward F. Plow ◽  
Tatiana V. Byzova
Keyword(s):  
Immune System ◽  
Essential Role ◽  
Recent Progress ◽  
Cellular Functions ◽  
Adhesion Receptors ◽  
Cell Matrix ◽  
Matrix Interactions ◽  
The Family ◽  
Intracellular Proteins ◽  
Cell Matrix Interactions

The Kindlin family of intracellular proteins has recently emerged as key regulators of cellular functions and cell-matrix interactions. The 3 members of this family, Kindlin-1, -2, and -3, perform an essential role in activation of integrin adhesion receptors, and expression of at least 1 Kindlin paralog is required to enable integrin activation in physiologically relevant settings. In humans, deficiencies in Kindlin-3 lead to a number of abnormalities affecting hemostasis, the immune system, and bone function, whereas the lack of Kindlin-1 causes profound skin defects. The importance of Kindlins is underscored by the results of animal knockout studies, which clearly show the indispensable and nonredundant functions of all 3 Kindlins in development and normal physiology. This review discusses recent progress in the studies of Kindlin protein family, emphasizing newly identified functions and potential mechanisms underlying differential activities of the family members.

scholarly journals Protein phosphatases in pancreatic islets

2014 ◽  
Vol 221 (3) ◽  
pp. R121-R144 ◽  
Author(s):  
Henrik Ortsäter ◽  
Nina Grankvist ◽  
Richard E Honkanen ◽  
Åke Sjöholm
Keyword(s):  
Molecular Mechanisms ◽  
Protein Phosphatases ◽  
Secretory Process ◽  
Cellular Functions ◽  
Β Cell ◽  
Intracellular Proteins ◽  
Protein Dephosphorylation ◽  
Stimulus Secretion Coupling ◽  
Hormonal Stimulus ◽  
Cardinal Feature

The prevalence of diabetes is increasing rapidly worldwide. A cardinal feature of most forms of diabetes is the lack of insulin-producing capability, due to the loss of insulin-producing β-cells, impaired glucose-sensitive insulin secretion from the β-cell, or a combination thereof, the reasons for which largely remain elusive. Reversible phosphorylation is an important and versatile mechanism for regulating the biological activity of many intracellular proteins, which, in turn, controls a variety of cellular functions. For instance, significant changes in protein kinase activities and in protein phosphorylation patterns occur subsequent to the stimulation of insulin release by glucose. Therefore, the molecular mechanisms regulating the phosphorylation of proteins involved in the insulin secretory process by the β-cell have been extensively investigated. However, far less is known about the role and regulation of protein dephosphorylation by various protein phosphatases. Herein, we review extant data implicating serine/threonine and tyrosine phosphatases in various aspects of healthy and diabetic islet biology, ranging from control of hormonal stimulus–secretion coupling to mitogenesis and apoptosis.

scholarly journals Molecular Crosstalk between Integrins and Cadherins: Do Reactive Oxygen Species Set the Talk?

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Luca Goitre ◽  
Barbara Pergolizzi ◽  
Elisa Ferro ◽  
Lorenza Trabalzini ◽  
Saverio Francesco Retta
Keyword(s):  
Reactive Oxygen Species ◽  
Cell Adhesion ◽  
Molecular Mechanisms ◽  
Immune Surveillance ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Functional Communication ◽  
Cellular Functions ◽  
Cell Matrix ◽  
Molecular Crosstalk

The coordinate modulation of the cellular functions of cadherins and integrins plays an essential role in fundamental physiological and pathological processes, including morphogenesis, tissue differentiation and renewal, wound healing, immune surveillance, inflammatory response, tumor progression, and metastasis. However, the molecular mechanisms underlying the fine-tuned functional communication between cadherins and integrins are still elusive. This paper focuses on recent findings towards the involvement of reactive oxygen species (ROS) in the regulation of cell adhesion and signal transduction functions of integrins and cadherins, pointing to ROS as emerging strong candidates for modulating the molecular crosstalk between cell-matrix and cell-cell adhesion receptors.

scholarly journals Vascular cell-matrix adhesion in development and cancer

2021 ◽  
Author(s):  
Christina Arapatzi ◽  
Georgia Rouni ◽  
Vassiliki Kostourou
Keyword(s):  
Endothelial Cells ◽  
Molecular Mechanisms ◽  
Notch Signalling ◽  
Tumour Angiogenesis ◽  
Genetic Studies ◽  
Cell Matrix ◽  
Vascular Morphogenesis ◽  
Current State ◽  
Cell Matrix Adhesion

The development and homeostasis of vertebrate organisms depend on the “tree of life”, that is the intricate network of vascular tubes composed by endothelial cells attached to the basement membrane and surrounded by perivascular cells. Although many studies have revealed the fundamental role of cytokines, growth factors and Notch signalling in vascular morphogenesis, we still lack sufficient understanding of the molecular mechanisms controlling the various steps of the angiogenic processes. Emerging data highlight that cell adhesions are key players in vascular morphogenesis. In this review, we focus on endothelial cells and we present the current state of knowledge regarding the role of cell-matrix adhesions in developmental and tumour angiogenesis, attained mainly from genetic studies and animal models.

scholarly journals Protein kinase Cα (PKCα) regulates the nucleocytoplasmic shuttling of KRIT1

2020 ◽  
pp. jcs.250217
Author(s):  
Elisa De Luca ◽  
Andrea Perrelli ◽  
Harsha Swamy ◽  
Mariapaola Nitti ◽  
Mario Passalacqua ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Molecular Mechanisms ◽  
Redox Homeostasis ◽  
Scaffolding Protein ◽  
Nuclear Accumulation ◽  
Nucleocytoplasmic Shuttling ◽  
Cell Matrix ◽  
Protein Kinase Cα ◽  
Subcellular Compartmentalization ◽  
Cell Matrix Adhesion

KRIT1 is a scaffolding protein that regulates multiple molecular mechanisms, including cell-cell and cell-matrix adhesion and redox homeostasis and signaling. However, rather little is known about how KRIT1 is itself regulated. KRIT1 is found in both the cytoplasm and the nucleus, yet the upstream signaling proteins and mechanisms that regulate KRIT1 nucleocytoplasmic shuttling are not well understood. Here, we identify a key role for protein kinase C (PKC). In particular, we found that PKC activation promotes the redox-dependent cytoplasmic localization of KRIT1, whereas inhibition of PKC or treatment with the antioxidant N-acetylcysteine leads to KRIT1 nuclear accumulation. Moreover, we demonstrated that the N-terminal region of KRIT1 is crucial for the ability of PKC to regulate KRIT1 nucleocytoplasmic shuttling, and may be a target for PKC-dependent regulatory phosphorylation events. Finally, we found that silencing of PKCα, but not PKCδ, inhibits phorbol-12-myristate-13-acetate (PMA)-induced cytoplasmic enrichment of KRIT1, suggesting a major role for PKCα in regulating KRIT1 nucleocytoplasmic shuttling. Overall, our findings identify PKCα as a novel regulator of KRIT1 subcellular compartmentalization, thus shedding new light on the physiopathological functions of this protein.

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