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Cell Motility and the Cytoskeleton 1990
Review
Topics: Actins; Animals; Contractile Proteins; Humans; Microfilament Proteins; Mutation; Profilins
PubMed: 2257632
DOI: 10.1002/cm.970170202 -
Biophysical Chemistry Feb 2016The path to the discovery of the actoclampins began with efforts to define profilin's role in actin-based pathogen and endosome rocketing. That research identified a set... (Review)
Review
The path to the discovery of the actoclampins began with efforts to define profilin's role in actin-based pathogen and endosome rocketing. That research identified a set of FPPPP-containing cargo proteins and FPPPP-binding proteins that are consistently stationed within the polymerization zone during episodes of active motility. The very same biophysical clues that forced us to abandon Brownian Ratchet models guided us to the Actoclampin Hypothesis, which asserts that every propulsive filament possesses a (+)-end-tracking motor that generates the forces cells need to crawl. Each actoclampin motor is a multi-arm oligomeric complex, employing one arm to recruit/deliver Profilin•Actin•ATP to a growth-site located at the (+)-end of the lagging subfilament, while a second arm maintains an affinity-modulated binding interaction with the extreme (+)-end of the other subfilament. The alternating actions of these arms define a true molecular motor, the processivity of which explains why propelling filaments maintain full possession of their cargo. The Actoclampin Hypothesis also suggests how the energetics of tracker interactions with the (+)-end determines whether a given actoclampin is a passive (low force-producing) or active (high force-producing) motor, the latter requiring the Gibbs free energy of ATP hydrolysis. Another aim of this review is to acknowledge an earlier notional model that emerged from efforts to comprehend profilin's pivotal role(s) in actin-based cell motility.
Topics: Actins; Cell Movement; Microfilament Proteins; Molecular Motor Proteins; Profilins
PubMed: 26720287
DOI: 10.1016/j.bpc.2015.10.008 -
The Journal of Cell Biology Dec 1994
Review
Topics: Actins; Animals; Carrier Proteins; Humans; Microfilament Proteins; Models, Biological; Movement; Muscles; Tropomodulin
PubMed: 7798305
DOI: 10.1083/jcb.127.6.1497 -
Developmental Cell Jul 2007The extent to which the many different pathways of endocytosis share underlying molecular mechanisms is currently unknown. In this issue of Developmental Cell, Yarar et... (Review)
Review
The extent to which the many different pathways of endocytosis share underlying molecular mechanisms is currently unknown. In this issue of Developmental Cell, Yarar et al. (2007) report that SNX9, a protein that binds phosphatidylinositides, dynamin, and N-WASP, coordinates actin assembly with several distinct endocytic processes.
Topics: Actins; Animals; Endocytosis; Microfilament Proteins
PubMed: 17609102
DOI: 10.1016/j.devcel.2007.06.005 -
Fascin-induced actin protrusions are suppressed by dendritic networks in giant unilamellar vesicles.Molecular Biology of the Cell Aug 2021The interactions between actin networks and cell membrane are immensely important for eukaryotic cell functions including cell shape changes, motility, polarity...
The interactions between actin networks and cell membrane are immensely important for eukaryotic cell functions including cell shape changes, motility, polarity establishment, and adhesion. Actin-binding proteins are known to compete and cooperate using a finite amount of actin monomers to form distinct actin networks. How actin-bundling protein fascin and actin-branching protein Arp2/3 complex compete to remodel membranes is not entirely clear. To investigate fascin- and Arp2/3-mediated actin network remodeling, we applied a reconstitution approach encapsulating bundled and dendritic actin networks inside giant unilamellar vesicles (GUVs). Independently reconstituted, membrane-bound Arp2/3 nucleation forms an actin cortex in GUVs, whereas fascin mediates formation of actin bundles that protrude out of GUVs. Coencapsulating both fascin and Arp2/3 complex leads to polarized dendritic aggregates and significantly reduces membrane protrusions, irrespective of whether the dendritic network is membrane bound or not. However, reducing Arp2/3 complex while increasing fascin restores membrane protrusion. Such changes in network assembly and the subsequent interplay with membrane can be attributed to competition between fascin and Arp2/3 complex to utilize a finite pool of actin.
Topics: Actin Cytoskeleton; Actin-Related Protein 2-3 Complex; Animals; Carrier Proteins; Microfilament Proteins; Phosphatidylcholines; Unilamellar Liposomes
PubMed: 34133215
DOI: 10.1091/mbc.E21-02-0080 -
Platelets 2013Recent findings have identified critical roles for the actin filament-crosslinking protein filamin A (FlnA) in platelets and megakaryocytes. This short review focuses on... (Review)
Review
Recent findings have identified critical roles for the actin filament-crosslinking protein filamin A (FlnA) in platelets and megakaryocytes. This short review focuses on the structure of FlnA and its interaction with the Von Willebrand Factor receptor GPIb-IX-V complex and the fibrinogen receptor, the integrin αIIbβ3 in platelets.
Topics: Blood Platelets; Carrier Proteins; Contractile Proteins; Filamins; Humans; Microfilament Proteins; Mutation; Protein Binding; Thrombocytopenia
PubMed: 22372530
DOI: 10.3109/09537104.2011.654004 -
Cell Structure and Function Dec 2023Directional cell rearrangement is a critical process underlying correct tissue deformation during morphogenesis. Although the involvement of F-actin regulation in cell...
Directional cell rearrangement is a critical process underlying correct tissue deformation during morphogenesis. Although the involvement of F-actin regulation in cell rearrangement has been established, the role and regulation of actin binding proteins (ABPs) in this process are not well understood. In this study, we investigated the function of Coronin-1, a WD-repeat actin-binding protein, in controlling directional cell rearrangement in the Drosophila pupal wing. Transgenic flies expressing Coronin-1-EGFP were generated using CRISPR-Cas9. We observed that Coronin-1 localizes at the reconnecting junction during cell rearrangement, which is dependent on actin interacting protein 1 (AIP1) and cofilin, actin disassemblers and known regulators of wing cell rearrangement. Loss of Coronin-1 function reduces cell rearrangement directionality and hexagonal cell fraction. These results suggest that Coronin-1 promotes directional cell rearrangement via its interaction with AIP1 and cofilin, highlighting the role of ABPs in the complex process of morphogenesis.Key words: morphogenesis, cell rearrangement, actin binding proteins (ABPs).
Topics: Animals; Drosophila; Microfilament Proteins; Actins; Actin Depolymerizing Factors; Epithelium
PubMed: 38030242
DOI: 10.1247/csf.23049 -
FEBS Letters Jan 2005Cortactin is an important molecular scaffold for actin assembly and organization. Novel mechanistic functions of cortactin have emerged with more interacting partners... (Review)
Review
Cortactin is an important molecular scaffold for actin assembly and organization. Novel mechanistic functions of cortactin have emerged with more interacting partners identified, revealing its multifaceted roles in regulating actin cytoskeletal networks that are necessary for endocytosis, cell migration and invasion, adhesion, synaptic organization and cell morphogenesis. These processes are mediated by its multi-domains binding to F-actin and Arp2/3 complex and various SH3 targets. Furthermore, its role in actin remodeling is subjected to regulation by tyrosine and serine/threonine kinases. Elucidating the mechanisms underlying cortactin phosphorylation and its functional consequences would provide new insights to various aspects of cell dynamics control.
Topics: Actins; Animals; Cortactin; Cytoskeleton; Endocytosis; Humans; Microfilament Proteins; Phosphorylation
PubMed: 15670811
DOI: 10.1016/j.febslet.2004.12.055 -
Cellular and Molecular Life Sciences :... Oct 2022In INF2-a formin linked to inherited renal and neurological disease in humans-the DID is preceded by a short N-terminal extension of unknown structure and function. INF2...
In INF2-a formin linked to inherited renal and neurological disease in humans-the DID is preceded by a short N-terminal extension of unknown structure and function. INF2 activation is achieved by Ca-dependent association of calmodulin (CaM). Here, we show that the N-terminal extension of INF2 is organized into two α-helices, the first of which is necessary to maintain the perinuclear F-actin ring and normal cytosolic F-actin content. Biochemical assays indicated that this helix interacts directly with CaM and contains the sole CaM-binding site (CaMBS) detected in INF2. The residues W11, L14 and L18 of INF2, arranged as a 1-4-8 motif, were identified as the most important residues for the binding, W11 being the most critical of the three. This motif is conserved in vertebrate INF2 and in the human population. NMR and biochemical analyses revealed that CaM interacts directly through its C-terminal lobe with the INF2 CaMBS. Unlike control cells, INF2 KO cells lacked the perinuclear F-actin ring, had little cytosolic F-actin content, did not respond to increased Ca concentrations by making more F-actin, and maintained the transcriptional cofactor MRTF predominantly in the cytoplasm. Whereas expression of intact INF2 restored all these defects, INF2 with inactivated CaMBS did not. Our study reveals the structure of the N-terminal extension, its interaction with Ca/CaM, and its function in INF2 activation.
Topics: Humans; Formins; Actins; Microfilament Proteins; Actin Cytoskeleton; Protein Binding
PubMed: 36306014
DOI: 10.1007/s00018-022-04581-y -
Biology Open Jun 2021Secreted proteins are transported along intracellular route from the endoplasmic reticulum through the Golgi before reaching the plasma membrane. Small GTPase Rab and...
Secreted proteins are transported along intracellular route from the endoplasmic reticulum through the Golgi before reaching the plasma membrane. Small GTPase Rab and their effectors play a key role in membrane trafficking. Using confocal microscopy, we showed that MICAL-L1 was associated with tubulo-vesicular structures and exhibited a significant colocalization with markers of the Golgi apparatus and recycling endosomes. Super resolution STORM microscopy suggested at the molecular level, a very close association of MICAL-L1 and microdomains in the Golgi cisternae. Using a synchronized secretion assay, we report that the shRNA-mediated depletion of MICAL-L1 impaired the delivery of a subset of cargo proteins to the cell surface. The process of membrane tubulation was monitored in vitro, and we observe that recombinant MICAL-L1-RBD domain may contribute to promote PACSINs-mediated membrane tubulation. Interestingly, two hydrophobic residues at the C-terminus of MICAL-L1 appeared to be important for phosphatidic acid binding, and for association with membrane tubules. Our results reveal a new role for MICAL-L1 in cargo delivery to the plasma membrane.
Topics: Amino Acids; Binding Sites; Cell Line; Cell Membrane; Fluorescent Antibody Technique; HeLa Cells; Humans; Immunohistochemistry; Microfilament Proteins; Mixed Function Oxygenases; Protein Binding; Protein Interaction Domains and Motifs; Protein Transport
PubMed: 34100897
DOI: 10.1242/bio.058008