Limits...
Mechanochemical regulation of growth cone motility.

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

Bottom Line: 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.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

Force generation and force sensing in neuronal growth cones. A neuronal growth cone is labeled for filamentous actin (red) and βI-II tubulin (green) using immunocytochemistry. This super resolution image was captured using structure illumination microscopy as previously described (Santiago-Medina et al., 2015). Overlaying the image are schematic elements depicting myosin dimers (purple) and adhesion complexes (yellow) near the central and peripheral growth cone, respectively. Myosin bound to actin produces a rearward force (purple arrows) on adhesion complexes where mechanosensitive (MS) proteins (parallel springs) detect this force. Adhesion complexes antagonize this rearward force allowing actin polymerization to expand the leading edge membrane (yellow arrows) and stretching a set of membrane MS proteins (perpendicular springs).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4493769&req=5

Figure 1: Force generation and force sensing in neuronal growth cones. A neuronal growth cone is labeled for filamentous actin (red) and βI-II tubulin (green) using immunocytochemistry. This super resolution image was captured using structure illumination microscopy as previously described (Santiago-Medina et al., 2015). Overlaying the image are schematic elements depicting myosin dimers (purple) and adhesion complexes (yellow) near the central and peripheral growth cone, respectively. Myosin bound to actin produces a rearward force (purple arrows) on adhesion complexes where mechanosensitive (MS) proteins (parallel springs) detect this force. Adhesion complexes antagonize this rearward force allowing actin polymerization to expand the leading edge membrane (yellow arrows) and stretching a set of membrane MS proteins (perpendicular springs).

Mentions: The cytomechanical forces that control growth cone motility have been intensely studied for the last 30 years, yet our understanding is still incomplete. Similar to non-neuronal cells, actin and microtubule polymerization play central roles as force-generating polymers in axonal growth cones (Figure 1). Complex mechanisms function within growth cones downstream of chemical and mechanical signals to tightly regulate the dynamic assembly and organization of the cytoskeleton (Lowery and van Vactor, 2009; Dent et al., 2011). Leading edge protrusion is thought to be driven largely by F-actin polymerization. Actin polymerization at the leading edge produces tensile forces, which are distributed between plasma membrane protrusion and rearward movement of F-actin bundles (Symons and Mitchison, 1991; Lin et al., 1996; Mogilner and Oster, 2003; Carlier and Pantaloni, 2007). Balance between membrane fluid dynamics and F-actin tensile strength may contribute to the extent of forward protrusion vs. rearward flow of F-actin (Figure 1; Bornschlögl, 2013). Conversely, ADF-cofilin mediated depolymerization of F-actin minus ends relieves compressive actin network forces and replenishes G-actin pools needed for further F-actin polymerization at the leading edge (Bamburg, 1999; Marsick et al., 2010; Zhang et al., 2012). A second force that powers F-actin retrograde flow (RF) is myosin-II motor dimers, which centripetally contract antiparallel F-actin networks toward the growth cone central domain (Turney and Bridgman, 2005; Medeiros et al., 2006; Yang et al., 2013; Shin et al., 2014). The contractile force of myosin-II, coupled with the rearward flow of F-actin due to leading edge polymerization, drives F-actin RF in growth cones (Forscher and Smith, 1988; Lin and Forscher, 1995; Brown and Bridgman, 2003). Other F-actin motor proteins, such as myosin I (Wang et al., 2003), V, VI (Suter et al., 2000; Kubota et al., 2010), and X (Berg and Cheney, 2002), also contribute to growth cone movements, morphology and vesicle trafficking.


Mechanochemical regulation of growth cone motility.

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

Force generation and force sensing in neuronal growth cones. A neuronal growth cone is labeled for filamentous actin (red) and βI-II tubulin (green) using immunocytochemistry. This super resolution image was captured using structure illumination microscopy as previously described (Santiago-Medina et al., 2015). Overlaying the image are schematic elements depicting myosin dimers (purple) and adhesion complexes (yellow) near the central and peripheral growth cone, respectively. Myosin bound to actin produces a rearward force (purple arrows) on adhesion complexes where mechanosensitive (MS) proteins (parallel springs) detect this force. Adhesion complexes antagonize this rearward force allowing actin polymerization to expand the leading edge membrane (yellow arrows) and stretching a set of membrane MS proteins (perpendicular springs).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Force generation and force sensing in neuronal growth cones. A neuronal growth cone is labeled for filamentous actin (red) and βI-II tubulin (green) using immunocytochemistry. This super resolution image was captured using structure illumination microscopy as previously described (Santiago-Medina et al., 2015). Overlaying the image are schematic elements depicting myosin dimers (purple) and adhesion complexes (yellow) near the central and peripheral growth cone, respectively. Myosin bound to actin produces a rearward force (purple arrows) on adhesion complexes where mechanosensitive (MS) proteins (parallel springs) detect this force. Adhesion complexes antagonize this rearward force allowing actin polymerization to expand the leading edge membrane (yellow arrows) and stretching a set of membrane MS proteins (perpendicular springs).
Mentions: The cytomechanical forces that control growth cone motility have been intensely studied for the last 30 years, yet our understanding is still incomplete. Similar to non-neuronal cells, actin and microtubule polymerization play central roles as force-generating polymers in axonal growth cones (Figure 1). Complex mechanisms function within growth cones downstream of chemical and mechanical signals to tightly regulate the dynamic assembly and organization of the cytoskeleton (Lowery and van Vactor, 2009; Dent et al., 2011). Leading edge protrusion is thought to be driven largely by F-actin polymerization. Actin polymerization at the leading edge produces tensile forces, which are distributed between plasma membrane protrusion and rearward movement of F-actin bundles (Symons and Mitchison, 1991; Lin et al., 1996; Mogilner and Oster, 2003; Carlier and Pantaloni, 2007). Balance between membrane fluid dynamics and F-actin tensile strength may contribute to the extent of forward protrusion vs. rearward flow of F-actin (Figure 1; Bornschlögl, 2013). Conversely, ADF-cofilin mediated depolymerization of F-actin minus ends relieves compressive actin network forces and replenishes G-actin pools needed for further F-actin polymerization at the leading edge (Bamburg, 1999; Marsick et al., 2010; Zhang et al., 2012). A second force that powers F-actin retrograde flow (RF) is myosin-II motor dimers, which centripetally contract antiparallel F-actin networks toward the growth cone central domain (Turney and Bridgman, 2005; Medeiros et al., 2006; Yang et al., 2013; Shin et al., 2014). The contractile force of myosin-II, coupled with the rearward flow of F-actin due to leading edge polymerization, drives F-actin RF in growth cones (Forscher and Smith, 1988; Lin and Forscher, 1995; Brown and Bridgman, 2003). Other F-actin motor proteins, such as myosin I (Wang et al., 2003), V, VI (Suter et al., 2000; Kubota et al., 2010), and X (Berg and Cheney, 2002), also contribute to growth cone movements, morphology and vesicle trafficking.

Bottom Line: 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.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