Trends in Cell Biology
ReviewCentrosome Special FocusEmerging roles for myosin II and cytoplasmic dynein in migrating neurons and growth cones
Introduction
Work over the past two decades has revealed that each of the three classes of cytoskeleton-associated motor proteins – the myosins, kinesins and dyneins – are represented in the higher eukaryotic genome by large gene families (Box 1). A major function of these proteins is in intracellular transport of membranous vesicles and macromolecular complexes. However, these proteins are also involved in basic aspects of cell movement and morphogenesis. Myosin II has long been understood to have a contractile role in muscle cells and in most other cell types but, until recently, there was little evidence of a role for microtubule-associated motors in cell translocation and other large scale cellular movements. Cytoplasmic dynein in particular was well known for its roles in subcellular transport. However, it has recently been implicated in several aspects of directed cell movement as well. Myosin II has been extensively studied for its role in fibroblast migration and growth cone extension. More recently, this motor protein has also been found to participate in neuronal migration. Cytoplasmic dynein and several of its regulatory factors, especially LIS1, NudE and NudEL (gene names Nde1 and Ndel1), have been implicated in neuronal migration from studies of brain developmental disease. A role for these proteins in growth-cone behavior and non-neuronal cell migration has also been identified. This article reviews recent evidence for a predominant role for myosin II and the major form of cytoplasmic dynein (MAP1C; dynein I) in neuronal migration and growth-cone function, with reference to studies in non-neuronal cells (Box 2). Despite the differential emphasis given to each of the two motor proteins in the several cellular systems that have been investigated, this review argues that myosin II and cytoplasmic dynein commonly act in concert to effect cell movement.
Section snippets
Behavior of migrating neurons
During development, neurons are generated within the germinal layers of the nervous system by the proliferation of progenitor cells. In the developing cerebrum (neocortex), pyramidal neurons are generated from radial glial progenitor cells (Box 3). These cells exhibit an extraordinary form of ‘interkinetic’ nuclear oscillations that are coordinated with cell-cycle progression. LIS1 RNAi in developing rat neocortex [1] and a dynactin mutation in zebra fish retina [2] have been found to interfere
Structural organization of the growth cone
The growth cone is a specialized structure involved in axonal elongation and pathfinding 21, 22 (Figure 2). It shares properties with other cellular domains such as lamellipodia and filopodia but has unique features as well. Although growth cones are morphologically dynamic, basic features of their organization are well established. Growth cones of neurons plated on artificial polyamine substrates are slow-advancing and tend to be well spread with a well-defined substructure. Actin filaments
Molecular models for myosin- and dynein-mediated cell movement
The data reviewed here indicate that myosin II and cytoplasmic dynein function in concert to carry out a variety of motile cell functions (Figure 2). Although the two motor proteins act in association with distinct cytoskeletal filaments, they do so in an interdependent fashion. Current data enable us to address in detail the sites at which the motor proteins function and reveal that their activities can be either antagonistic or cooperative in different neuronal cell contexts.
Concluding remarks
Myosin II and cytoplasmic dynein have emerged as major players in non-neuronal cell migration, neuronal migration and growth-cone motility (Figure 2). Myosin II has an expected contractile role in these cellular contexts, although at different cellular sites in each case and in a far less highly organized manner than in striated muscle cells. Cytoplasmic dynein exerts its effects on cell movement not through retrograde cargo transport but, rather, through exertion of equal and opposite forces
Acknowledgements
We thank Mary Beth Hatten, Bruce Schaar, Susan McConnell and Paul Forscher for providing images for this article, and Silvia Cappello, Wei-Nan Lian, Timothy Petros, Richard McKenney and Kassandra Ori for critical reading of the manuscript and helpful suggestions. This work was supported by NIH Grants HD40182 and GM47434 and the March of Dimes Birth Defects Foundation.
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