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Mechanochemical regulation of growth cone motility.

Kerstein PC, Nichol RH, Gomez TM - Front Cell Neurosci (2015)

Bottom Line: Extensive research has shown that chemical ligands activate cell surface receptors on growth cones leading to intracellular signals that direct cytoskeletal changes.Interestingly, recent work suggests that both the mechanical properties of the environment and mechanical forces generated within growth cones influence axon guidance.In this review we discuss novel molecular mechanisms involved in growth cone force production and detection, and speculate how these processes may be necessary for the development of proper neuronal morphogenesis.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Training Program, Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin-Madison Madison, WI, USA.

ABSTRACT
Neuronal growth cones are exquisite sensory-motor machines capable of transducing features contacted in their local extracellular environment into guided process extension during development. Extensive research has shown that chemical ligands activate cell surface receptors on growth cones leading to intracellular signals that direct cytoskeletal changes. However, the environment also provides mechanical support for growth cone adhesion and traction forces that stabilize leading edge protrusions. Interestingly, recent work suggests that both the mechanical properties of the environment and mechanical forces generated within growth cones influence axon guidance. In this review we discuss novel molecular mechanisms involved in growth cone force production and detection, and speculate how these processes may be necessary for the development of proper neuronal morphogenesis.

No MeSH data available.


Related in: MedlinePlus

Mechanotranduction within growth cone filopodia involves adhesion and Ca2+ signaling. (1) Formation of point contact adhesions are initiated by talin-dependent inside-out activation of integrin receptors. (2) Point contact adhesions form when integrins bind to the ECM and intracellular proteins, such as FAK and paxillin, are recruited to signal and link integrins to the actin cytoskeleton. MS proteins, such as FAK, Talin, and CAS (not shown), are activated during substratum rigidity sensing and signaling for adhesion maturation. (3) Additional proteins are recruited during adhesion maturation, such as vinculin and the actin nucleator Arp2/3. Therefore, mature adhesions act as a signaling nexus for new actin filament polymerization off existing filaments, leading to veil protrusion. (4) Adhesion assembly and maturation can be disrupted when Ca2+ flows through MS channels (MSC). Ca2+ ions directly activate the protease calpain that targets specific adhesion proteins to inhibit or modulate their function (Kerstein et al., 2013).
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Figure 4: Mechanotranduction within growth cone filopodia involves adhesion and Ca2+ signaling. (1) Formation of point contact adhesions are initiated by talin-dependent inside-out activation of integrin receptors. (2) Point contact adhesions form when integrins bind to the ECM and intracellular proteins, such as FAK and paxillin, are recruited to signal and link integrins to the actin cytoskeleton. MS proteins, such as FAK, Talin, and CAS (not shown), are activated during substratum rigidity sensing and signaling for adhesion maturation. (3) Additional proteins are recruited during adhesion maturation, such as vinculin and the actin nucleator Arp2/3. Therefore, mature adhesions act as a signaling nexus for new actin filament polymerization off existing filaments, leading to veil protrusion. (4) Adhesion assembly and maturation can be disrupted when Ca2+ flows through MS channels (MSC). Ca2+ ions directly activate the protease calpain that targets specific adhesion proteins to inhibit or modulate their function (Kerstein et al., 2013).

Mentions: For cells to sense the mechanical properties of their environment they must express proteins that change their conformation in response to mechanical force or tension. Depending on the type of mechanosensitive (MS) protein, conformational changes may lead to modulation of enzymatic activity, accessibility of binding sites for protein-protein interactions, or regulation of ion channel gating. One site where cell mechanosensors are likely concentrated is at integrin receptor-adhesion protein complexes, which function at the interface between the cytoskeleton and ECM (Figure 4). Adhesion complexes are spatially and temporally regulated by mechanical strain and substrate elasticity (Pelham and Wang, 1997; Schedin and Keely, 2011), suggesting they provide homeostatic feedback, termed tensional homeostasis. In this section we will discuss several recent reports that demonstrate that individual adhesion proteins and MS ion channels can respond to mechanical forces (Table 1).


Mechanochemical regulation of growth cone motility.

Kerstein PC, Nichol RH, Gomez TM - Front Cell Neurosci (2015)

Mechanotranduction within growth cone filopodia involves adhesion and Ca2+ signaling. (1) Formation of point contact adhesions are initiated by talin-dependent inside-out activation of integrin receptors. (2) Point contact adhesions form when integrins bind to the ECM and intracellular proteins, such as FAK and paxillin, are recruited to signal and link integrins to the actin cytoskeleton. MS proteins, such as FAK, Talin, and CAS (not shown), are activated during substratum rigidity sensing and signaling for adhesion maturation. (3) Additional proteins are recruited during adhesion maturation, such as vinculin and the actin nucleator Arp2/3. Therefore, mature adhesions act as a signaling nexus for new actin filament polymerization off existing filaments, leading to veil protrusion. (4) Adhesion assembly and maturation can be disrupted when Ca2+ flows through MS channels (MSC). Ca2+ ions directly activate the protease calpain that targets specific adhesion proteins to inhibit or modulate their function (Kerstein et al., 2013).
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4493769&req=5

Figure 4: Mechanotranduction within growth cone filopodia involves adhesion and Ca2+ signaling. (1) Formation of point contact adhesions are initiated by talin-dependent inside-out activation of integrin receptors. (2) Point contact adhesions form when integrins bind to the ECM and intracellular proteins, such as FAK and paxillin, are recruited to signal and link integrins to the actin cytoskeleton. MS proteins, such as FAK, Talin, and CAS (not shown), are activated during substratum rigidity sensing and signaling for adhesion maturation. (3) Additional proteins are recruited during adhesion maturation, such as vinculin and the actin nucleator Arp2/3. Therefore, mature adhesions act as a signaling nexus for new actin filament polymerization off existing filaments, leading to veil protrusion. (4) Adhesion assembly and maturation can be disrupted when Ca2+ flows through MS channels (MSC). Ca2+ ions directly activate the protease calpain that targets specific adhesion proteins to inhibit or modulate their function (Kerstein et al., 2013).
Mentions: For cells to sense the mechanical properties of their environment they must express proteins that change their conformation in response to mechanical force or tension. Depending on the type of mechanosensitive (MS) protein, conformational changes may lead to modulation of enzymatic activity, accessibility of binding sites for protein-protein interactions, or regulation of ion channel gating. One site where cell mechanosensors are likely concentrated is at integrin receptor-adhesion protein complexes, which function at the interface between the cytoskeleton and ECM (Figure 4). Adhesion complexes are spatially and temporally regulated by mechanical strain and substrate elasticity (Pelham and Wang, 1997; Schedin and Keely, 2011), suggesting they provide homeostatic feedback, termed tensional homeostasis. In this section we will discuss several recent reports that demonstrate that individual adhesion proteins and MS ion channels can respond to mechanical forces (Table 1).

Bottom Line: Extensive research has shown that chemical ligands activate cell surface receptors on growth cones leading to intracellular signals that direct cytoskeletal changes.Interestingly, recent work suggests that both the mechanical properties of the environment and mechanical forces generated within growth cones influence axon guidance.In this review we discuss novel molecular mechanisms involved in growth cone force production and detection, and speculate how these processes may be necessary for the development of proper neuronal morphogenesis.

View Article: PubMed Central - PubMed

Affiliation: Neuroscience Training Program, Department of Neuroscience, School of Medicine and Public Health, University of Wisconsin-Madison Madison, WI, USA.

ABSTRACT
Neuronal growth cones are exquisite sensory-motor machines capable of transducing features contacted in their local extracellular environment into guided process extension during development. Extensive research has shown that chemical ligands activate cell surface receptors on growth cones leading to intracellular signals that direct cytoskeletal changes. However, the environment also provides mechanical support for growth cone adhesion and traction forces that stabilize leading edge protrusions. Interestingly, recent work suggests that both the mechanical properties of the environment and mechanical forces generated within growth cones influence axon guidance. In this review we discuss novel molecular mechanisms involved in growth cone force production and detection, and speculate how these processes may be necessary for the development of proper neuronal morphogenesis.

No MeSH data available.


Related in: MedlinePlus