The Myosin Va Head Domain Binds to the Neurofilament-L Rod and Modulates Endoplasmic Reticulum (ER) Content and Distribution within Axons

The neurofilament light subunit (NF-L) binds to myosin Va (Myo Va) in neurons but the sites of interaction and functional significance are not clear. We show by deletion analysis that motor domain of Myo Va binds to the NF-L rod domain that forms the NF backbone. Loss of NF-L and Myo Va binding from axons significantly reduces the axonal content of ER, and redistributes ER to the periphery of axon. Our data are consistent with a novel function for NFs as a scaffold in axons for maintaining the content and proper distribution of vesicular organelles, mediated in part by Myo Va. Based on observations that the Myo Va motor domain binds to intermediate filament (IF) proteins of several classes, Myo Va interactions with IFs may serve similar roles in organizing organelle topography in different cell types.

[1]  Vivek V. Kanumuri,et al.  Neurofilaments Form a Highly Stable Stationary Cytoskeleton after Reaching a Critical Level in Axons , 2009, The Journal of Neuroscience.

[2]  Peter Jung,et al.  Myosin Va Increases the Efficiency of Neurofilament Transport by Decreasing the Duration of Long-Term Pauses , 2009, The Journal of Neuroscience.

[3]  V. Haroutunian,et al.  Marked Calpastatin (CAST) Depletion in Alzheimer's Disease Accelerates Cytoskeleton Disruption and Neurodegeneration: Neuroprotection by CAST Overexpression , 2008, The Journal of Neuroscience.

[4]  Mark Ellisman,et al.  Electron tomographic analysis of cytoskeletal cross-bridges in the paranodal region of the node of Ranvier in peripheral nerves. , 2008, Journal of structural biology.

[5]  Samara L. Reck-Peterson,et al.  Myo2p, a class V myosin in budding yeast, associates with a large ribonucleic acid-protein complex that contains mRNAs and subunits of the RNA-processing body. , 2008, RNA.

[6]  H. Lung,et al.  Vimentin supports mitochondrial morphology and organization. , 2008, The Biochemical journal.

[7]  Aidong Yuan,et al.  Axonal Transport Rates In Vivo Are Unaffected by Tau Deletion or Overexpression in Mice , 2008, The Journal of Neuroscience.

[8]  Ilya Zaliapin,et al.  Switching of membrane organelles between cytoskeletal transport systems is determined by regulation of the microtubule-based transport , 2007, The Journal of cell biology.

[9]  P. Coulombe,et al.  Intermediate filament scaffolds fulfill mechanical, organizational, and signaling functions in the cytoplasm. , 2007, Genes & development.

[10]  M. Mavroidis,et al.  Muscle intermediate filaments and their links to membranes and membranous organelles. , 2007, Experimental cell research.

[11]  A. Sonnenberg,et al.  Plakins in development and disease. , 2007, Experimental cell research.

[12]  Jean-Pierre Julien,et al.  Conditional NF-L Transgene Expression in Mice for In Vivo Analysis of Turnover and Transport Rate of Neurofilaments , 2007, The Journal of Neuroscience.

[13]  Paul R. Selvin,et al.  Tracking melanosomes inside a cell to study molecular motors and their interaction , 2007, Proceedings of the National Academy of Sciences.

[14]  Thomas D. Pollard,et al.  Myosin Va maneuvers through actin intersections and diffuses along microtubules , 2007, Proceedings of the National Academy of Sciences.

[15]  T. Takumi,et al.  Myosin-Va Facilitates the Accumulation of mRNA/Protein Complex in Dendritic Spines , 2006, Current Biology.

[16]  K. Schlett,et al.  Alternatively spliced exon B of myosin Va is essential for binding the tail-associated light chain shared by dynein. , 2006, Biochemistry.

[17]  Veeranna,et al.  α-Internexin Is Structurally and Functionally Associated with the Neurofilament Triplet Proteins in the Mature CNS , 2006, The Journal of Neuroscience.

[18]  Yui Jin,et al.  Structural basis for myosin V discrimination between distinct cargoes , 2006, The EMBO journal.

[19]  T. Ushiki,et al.  Myosin-Va regulates exocytosis through the submicromolar Ca2+-dependent binding of syntaxin-1A. , 2005, Molecular biology of the cell.

[20]  V. Faundez,et al.  The endo-lysosomal sorting machinery interacts with the intermediate filament cytoskeleton. , 2004, Molecular biology of the cell.

[21]  T. Shea,et al.  Neurofilament Transport Is Dependent on Actin and Myosin , 2004, The Journal of Neuroscience.

[22]  K. Steel,et al.  Myosin Va is required for normal photoreceptor synaptic activity , 2004, Journal of Cell Science.

[23]  J. Julien,et al.  Neurofilament Transport In Vivo Minimally Requires Hetero-Oligomer Formation , 2003, The Journal of Neuroscience.

[24]  G. Langford.  Myosin‐V, a Versatile Motor for Short‐Range Vesicle Transport , 2002, Traffic.

[25]  J. Julien,et al.  Myosin Va binding to neurofilaments is essential for correct myosin Va distribution and transport and neurofilament density , 2002, The Journal of cell biology.

[26]  R. Cheney,et al.  Human myosin-Vc is a novel class V myosin expressed in epithelial cells. , 2002, Journal of cell science.

[27]  D. Suter,et al.  The light chain composition of chicken brain myosin-Va: calmodulin, myosin-II essential light chains, and 8-kDa dynein light chain/PIN. , 2000, Cell motility and the cytoskeleton.

[28]  Lei Wang,et al.  Rapid movement of axonal neurofilaments interrupted by prolonged pauses , 2000, Nature Cell Biology.

[29]  R. Liem,et al.  Microtubule Actin Cross-Linking Factor (Macf) , 1999, The Journal of cell biology.

[30]  Oliver Tn,et al.  Tails of unconventional myosins. , 1999 .

[31]  P. Bridgman.  Myosin VA Movements in Normal and Dilute-Lethal Axons Provide Support for a Dual Filament Motor Complex , 1999, The Journal of cell biology.

[32]  Matthias Rief,et al.  Myosin-V is a processive actin-based motor , 1999, Nature.

[33]  E. M. Espreafico,et al.  Brain Myosin-V, a Calmodulin-carrying Myosin, Binds to Calmodulin-dependent Protein Kinase II and Activates Its Kinase Activity* , 1999, The Journal of Biological Chemistry.

[34]  K. Weber,et al.  Molecular Phylogeny of Metazoan Intermediate Filament Proteins , 1998, Journal of Molecular Evolution.

[35]  Q. Zhu,et al.  Absence of neurofilaments reduces the selective vulnerability of motor neurons and slows disease caused by a familial amyotrophic lateral sclerosis-linked superoxide dismutase 1 mutant. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[36]  M. Mooseker,et al.  Vesicle-associated brain myosin-V can be activated to catalyze actin-based transport. , 1998, Journal of cell science.

[37]  E. Fuchs,et al.  A structural scaffolding of intermediate filaments in health and disease. , 1998, Science.

[38]  J. Julien,et al.  Delayed Maturation of Regenerating Myelinated Axons in Mice Lacking Neurofilaments , 1997, Experimental Neurology.

[39]  A. Fischer,et al.  Griscelli disease maps to chromosome 15q21 and is associated with mutations in the Myosin-Va gene , 1997, Nature Genetics.

[40]  Q. Wei,et al.  Myosin V associates with melanosomes in mouse melanocytes: evidence that myosin V is an organelle motor. , 1997, Journal of cell science.

[41]  L. Engle,et al.  Cloning, analysis, and chromosomal localization of myoxin (MYH12), the human homologue to the mouse dilute gene. , 1994, Genomics.

[42]  P. De Camilli,et al.  Primary structure and cellular localization of chicken brain myosin-V (p190), an unconventional myosin with calmodulin light chains , 1992, The Journal of cell biology.

[43]  G. C. Johnston,et al.  The Saccharomyces cerevisiae MYO2 gene encodes an essential myosin for vectorial transport of vesicles , 1991, The Journal of cell biology.

[44]  N. Copeland,et al.  Dilute suppressor dsu acts semidominantly to suppress the coat color phenotype of a deletion mutation, dl20J, of the murine dilute locus. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[45]  G. Wise,et al.  Sodium dodecyl sulfate-gel electrophoresis: staining of polypeptides using heavy metal salts. , 1988, Analytical biochemistry.

[46]  S. Lewis,et al.  Anomalous placement of introns in a member of the intermediate filament multigene family: an evolutionary conundrum , 1986, Molecular and cellular biology.

[47]  R. Nixon,et al.  Multiple fates of newly synthesized neurofilament proteins: evidence for a stationary neurofilament network distributed nonuniformly along axons of retinal ganglion cell neurons , 1986, The Journal of cell biology.

[48]  J. Pachter,et al.  A batchwise purification procedure of neurofilament proteins. , 1983, Analytical biochemistry.

[49]  J. Julien,et al.  The distribution of phosphorylation sites among identified proteolytic fragments of mammalian neurofilaments. , 1983, The Journal of biological chemistry.

[50]  S. Schmidt,et al.  Tissue processing prior to protein analysis and amyloid-beta quantitation. , 2005, Methods in molecular biology.

[51]  S. Schmidt,et al.  Tissue Processing Prior to Protein Analysis and Amyloid-ß Quantitation , 2005 .

[52]  T. N. Oliver,et al.  Tails of unconventional myosins , 1999, Cellular and Molecular Life Sciences CMLS.

[53]  J. Tímár,et al.  PKC mediates 12(S)-HETE-induced cytoskeletal rearrangement in B16a melanoma cells. , 1993, Cell motility and the cytoskeleton.

[54]  N. Copeland,et al.  Novel myosin heavy chain encoded by murine dilute coat colour locus , 1991, Nature.