scholarly journals Dia1 and IQGAP1 interact in cell migration and phagocytic cup formation

2007 ◽  
Vol 178 (2) ◽  
pp. 193-200 ◽  
Author(s):  
Dominique T. Brandt ◽  
Sabrina Marion ◽  
Gareth Griffiths ◽  
Takashi Watanabe ◽  
Kozo Kaibuchi ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Filament ◽  
Cell Shape ◽  
Actin Polymerization ◽  
Binding Protein ◽  
Subcellular Location ◽  
Scaffold Protein ◽  
Cellular Location ◽  
Inhibitory Domain ◽  
Migrating Cells

The Diaphanous-related formin Dia1 nucleates actin polymerization, thereby regulating cell shape and motility. Mechanisms that control the cellular location of Dia1 to spatially define actin polymerization are largely unknown. In this study, we identify the cytoskeletal scaffold protein IQGAP1 as a Dia1-binding protein that is necessary for its subcellular location. IQGAP1 interacts with Dia1 through a region within the Diaphanous inhibitory domain after the RhoA-mediated release of Dia1 autoinhibition. Both proteins colocalize at the front of migrating cells but also at the actin-rich phagocytic cup in macrophages. We show that IQGAP1 interaction with Dia1 is required for phagocytosis and phagocytic cup formation. Thus, we identify IQGAP1 as a novel component involved in the regulation of phagocytosis by mediating the localization of the actin filament nucleator Dia1.

scholarly journals Frabin, a Novel FGD1-related Actin Filament-binding Protein Capable of Changing Cell Shape and Activating c-Jun N-terminal Kinase

1998 ◽  
Vol 273 (30) ◽  
pp. 18697-18700 ◽  
Author(s):  
Hiroshi Obaishi ◽  
Hiroyuki Nakanishi ◽  
Kenji Mandai ◽  
Keiko Satoh ◽  
Ayako Satoh ◽  
...  
Keyword(s):  
Actin Filament ◽  
Cell Shape ◽  
Binding Protein

scholarly journals Actin-inspired feedback couples speed and persistence in a Cellular Potts Model of cell migration

2018 ◽  
Author(s):  
Inge M. N. Wortel ◽  
Ioana Niculescu ◽  
P. Martijn Kolijn ◽  
Nir Gov ◽  
Rob J. de Boer ◽  
...  
Keyword(s):  
Cell Migration ◽  
Cell Motility ◽  
Potts Model ◽  
Cell Shape ◽  
Computational Models ◽  
Fundamental Property ◽  
Cellular Potts Model ◽  
Universal Coupling ◽  
Migrating Cells

ABSTRACTCell migration is astoundingly diverse. Molecular signatures, cell-cell and cell-matrix interactions, and environmental structures each play their part in shaping cell motion, yielding numerous different cell morphologies and migration modes. Nevertheless, in recent years, a simple unifying law was found to describe cell migration across many different cell types and contexts: faster cells turn less frequently. Given this universal coupling between speed and persistence (UCSP), from a modelling perspective it is important to know whether computational models of cell migration capture this speed-persistence link. Here, we present an in-depth characterisation of an existing Cellular Potts Model (CPM). We first show that this model robustly reproduces the UCSP without having been designed for this task. Instead, we show that this fundamental law of migration emerges spontaneously through a crosstalk of intracellular mechanisms, cell shape, and environmental constraints, resembling the dynamic nature of cell migration in vivo. Our model also reveals how cell shape dynamics can further constrain cell motility by limiting both the speed and persistence a cell can reach, and how a rigid environment such as the skin can restrict cell motility even further. Our results further validate the CPM as a model of cell migration, and shed new light on the speed-persistence coupling that has emerged as a fundamental property of migrating cells.SIGNIFICANCEThe universal coupling between speed and persistence (UCSP) is the first general quantitative law describing motility patterns across the versatile spectrum of migrating cells. Here, we show – for the first time – that this migration law emerges spontaneously in an existing, highly popular computational model of cell migration. Studying the UCSP in entirely different model frameworks, not explicitly built with this law in mind, can help uncover how intracellular dynamics, cell shape, and environment interact to produce the diverse motility patterns observed in migrating cells.

scholarly journals Nascent adhesions differentially regulate lamellipodium velocity and persistence

2021 ◽  
Author(s):  
Keith R Carney ◽  
Akib M Khan ◽  
Shiela C Samson ◽  
Nikhil Mittal ◽  
Sangyoon J Han ◽  
...  
Keyword(s):  
Cell Migration ◽  
Computational Model ◽  
Actin Filament ◽  
Actin Polymerization ◽  
Leading Edge ◽  
Membrane Tension ◽  
Cell Edge ◽  
Ratchet Mechanism ◽  
Model Predictions ◽  
Clutch Mechanism

Cell migration is essential to physiological and pathological biology. Migration is driven by the motion of a leading edge, in which actin polymerization pushes against the edge and adhesions transmit traction to the substrate while membrane tension increases. How the actin and adhesions synergistically control edge protrusion remains elusive. We addressed this question by developing a computational model in which the Brownian ratchet mechanism governs actin filament polymerization against the membrane and the molecular clutch mechanism governs adhesion to the substrate (BR-MC model). Our model predicted that actin polymerization is the most significant driver of protrusion, as actin had a greater effect on protrusion than adhesion assembly. Increasing the lifetime of nascent adhesions also enhanced velocity, but decreased the protrusion's motional persistence, because filaments maintained against the cell edge ceased polymerizing as membrane tension increased. We confirmed the model predictions with measurement of adhesion lifetime and edge motion in migrating cells. Adhesions with longer lifetime were associated with faster protrusion velocity and shorter persistence. Experimentally increasing adhesion lifetime increased velocity but decreased persistence. We propose a mechanism for actin polymerization-driven, adhesion-dependent protrusion in which balanced nascent adhesion assembly and lifetime generates protrusions with the power and persistence to drive migration.

scholarly journals Spatial confinement of receptor activity by tyrosine phosphatase during directional cell migration

2020 ◽  
Vol 117 (25) ◽  
pp. 14270-14279
Author(s):  
Zhiwen Zhu ◽  
Yongping Chai ◽  
Huifang Hu ◽  
Wei Li ◽  
Wen-Jun Li ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Polymerization ◽  
Transmembrane Protein ◽  
Tyrosine Phosphatase ◽  
Leading Edge ◽  
Receptor Activity ◽  
Actin Assembly ◽  
Neuroblast Migration ◽  
Directional Cell Migration ◽  
Migrating Cells

Directional cell migration involves signaling cascades that stimulate actin assembly at the leading edge, and additional pathways must inhibit actin polymerization at the rear. During neuroblast migration inCaenorhabditis elegans, the transmembrane protein MIG-13/Lrp12 acts through the Arp2/3 nucleation-promoting factors WAVE and WASP to guide the anterior migration. Here we show that a tyrosine kinase, SRC-1, directly phosphorylates MIG-13 and promotes its activity on actin assembly at the leading edge. In GFP knockin animals, SRC-1 and MIG-13 distribute along the entire plasma membrane of migrating cells. We reveal that a receptor-like tyrosine phosphatase, PTP-3, maintains the F-actin polarity during neuroblast migration. Recombinant PTP-3 dephosphorylates SRC-1–dependent MIG-13 phosphorylation in vitro. Importantly, the endogenous PTP-3 accumulates at the rear of the migrating neuroblast, and its extracellular domain is essential for directional cell migration. We provide evidence that the asymmetrically localized tyrosine phosphatase PTP-3 spatially restricts MIG-13/Lrp12 receptor activity in migrating cells.

scholarly journals Regulated Interactions between Dynamin and the Actin-Binding Protein Cortactin Modulate Cell Shape

2000 ◽  
Vol 151 (1) ◽  
pp. 187-198 ◽  
Author(s):  
Mark A. McNiven ◽  
Leung Kim ◽  
Eugene W. Krueger ◽  
James D. Orth ◽  
Hong Cao ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Cytoskeleton ◽  
Cell Shape ◽  
Binding Protein ◽  
Sh3 Domain ◽  
Actin Binding ◽  
Coat Proteins ◽  
Actin Binding Protein ◽  
Morphological Studies

The dynamin family of large GTPases has been implicated in the formation of nascent vesicles in both the endocytic and secretory pathways. It is believed that dynamin interacts with a variety of cellular proteins to constrict membranes. The actin cytoskeleton has also been implicated in altering membrane shape and form during cell migration, endocytosis, and secretion and has been postulated to work synergistically with dynamin and coat proteins in several of these important processes. We have observed that the cytoplasmic distribution of dynamin changes dramatically in fibroblasts that have been stimulated to undergo migration with a motagen/hormone. In quiescent cells, dynamin 2 (Dyn 2) associates predominantly with clathrin-coated vesicles at the plasma membrane and the Golgi apparatus. Upon treatment with PDGF to induce cell migration, dynamin becomes markedly associated with membrane ruffles and lamellipodia. Biochemical and morphological studies using antibodies and GFP-tagged dynamin demonstrate an interaction with cortactin. Cortactin is an actin-binding protein that contains a well defined SH3 domain. Using a variety of biochemical methods we demonstrate that the cortactin–SH3 domain associates with the proline-rich domain (PRD) of dynamin. Functional studies that express wild-type and mutant forms of dynamin and/or cortactin in living cells support these in vitro observations and demonstrate that an increased expression of cortactin leads to a significant recruitment of endogenous or expressed dynamin into the cell ruffle. Further, expression of a cortactin protein lacking the interactive SH3 domain (CortΔSH3) significantly reduces dynamin localization to the ruffle. Accordingly, transfected cells expressing Dyn 2 lacking the PRD (Dyn 2(aa)ΔPRD) sequester little of this protein to the cortactin-rich ruffle. Interestingly, these mutant cells are viable, but display dramatic alterations in morphology. This change in shape appears to be due, in part, to a striking increase in the number of actin stress fibers. These findings provide the first demonstration that dynamin can interact with the actin cytoskeleton to regulate actin reorganization and subsequently cell shape.

scholarly journals A WASp-binding type II phosphatidylinositol 4-kinase required for actin polymerization-driven endosome motility

2005 ◽  
Vol 171 (1) ◽  
pp. 133-142 ◽  
Author(s):  
Fanny S. Chang ◽  
Gil-Soo Han ◽  
George M. Carman ◽  
Kendall J. Blumer
Keyword(s):  
Plasma Membrane ◽  
Actin Filament ◽  
Actin Polymerization ◽  
Binding Protein ◽  
Type Ii ◽  
Activation Domain ◽  
Cargo Protein ◽  
Phosphatidylinositol 4 ◽  
Syndrome Protein ◽  
Binding Type

Endosomes in yeast have been hypothesized to move through the cytoplasm by the momentum gained after actin polymerization has driven endosome abscision from the plasma membrane. Alternatively, after abscission, ongoing actin polymerization on endosomes could power transport. Here, we tested these hypotheses by showing that the Arp2/3 complex activation domain (WCA) of Las17 (Wiskott-Aldrich syndrome protein [WASp] homologue) fused to an endocytic cargo protein (Ste2) rescued endosome motility in las17ΔWCA mutants, and that capping actin filament barbed ends inhibited endosome motility but not endocytic internalization. Motility therefore requires continual actin polymerization on endosomes. We also explored how Las17 is regulated. Endosome motility required the Las17-binding protein Lsb6, a type II phosphatidylinositol 4-kinase. Catalytically inactive Lsb6 interacted with Las17 and promoted endosome motility. Lsb6 therefore is a novel regulator of Las17 that mediates endosome motility independent of phosphatidylinositol 4-phosphate synthesis. Mammalian type II phosphatidylinositol 4-kinases may regulate WASp proteins and endosome motility.

scholarly journals Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation

2019 ◽  
Author(s):  
Georgi Dimchev ◽  
Behnam Amiri ◽  
Ashley C. Humphries ◽  
Matthias Schaks ◽  
Vanessa Dimchev ◽  
...  
Keyword(s):  
Cell Migration ◽  
Actin Polymerization ◽  
Binding Protein ◽  
Critical Role ◽  
Adhesion Formation ◽  
Leading Edge ◽  
Actin Binding ◽  
Membrane Ruffling ◽  
Genetic Ablation ◽  
And Migration

ABSTRACTEfficient migration on adhesive surfaces involves the protrusion of lamellipodial actin networks and their subsequent stabilization by nascent adhesions. The actin binding protein lamellipodin (Lpd) is thought to play a critical role in lamellipodium protrusion, by delivering Ena/VASP proteins onto the growing plus ends of actin filaments and by interacting with the WAVE regulatory complex (WRC), an activator of the Arp2/3 complex, at the leading edge. Using B16-F1 melanoma cell lines, we demonstrate that genetic ablation of Lpd compromises protrusion efficiency and coincident cell migration without altering essential parameters of lamellipodia, including their maximal rate of forward advancement and actin polymerization. We also confirmed lamellipodia and migration phenotypes with CRISPR/Cas9-mediated Lpd knockout Rat2 fibroblasts, excluding cell type-specific effects. Moreover, computer-aided analysis of cell edge morphodynamics on B16-F1 cell lamellipodia revealed that loss of Lpd correlates with reduced temporal protrusion maintenance as a prerequisite of nascent adhesion formation. We conclude that Lpd optimizes protrusion and nascent adhesion formation by counteracting frequent, chaotic retraction and membrane ruffling.Summary statementWe describe how genetic ablation of the prominent actin- and VASP-binding protein lamellipodin combined with software-aided protrusion analysis uncovers mechanistic insights into its cellular function during cell migration.

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