Dominant-Negative Myosin Va Impairs Retrograde but Not Anterograde Axonal Transport of Large Dense Core Vesicles

• Published in: Cellular and molecular neurobiology Vol. 30; no. 3; pp. 369 - 379
• Main Authors: Bittins, Claudia Margarethe, Eichler, Tilo Wolf, Hammer, John A. III, Gerdes, Hans-Hermann
• Format: Journal Article
• Language: English
• Published: Boston Boston : Springer US 01.04.2010; Springer US
• Subjects: Actin Cytoskeleton - metabolism; Actin Cytoskeleton - ultrastructure; Animals; Axonal Transport - physiology; Axons - metabolism; Axons - ultrastructure; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cells, Cultured; Green Fluorescent Proteins - genetics; Green Fluorescent Proteins - metabolism; Hippocampus - metabolism; Hippocampus - ultrastructure; Image Cytometry; Microtubules - metabolism; Microtubules - ultrastructure; Models, Biological; Molecular Motor Proteins - metabolism; Myosin Heavy Chains - metabolism; Myosin Type V - metabolism; Neurobiology; Neuropeptide Y - genetics; Neuropeptide Y - metabolism; Neurosciences; Original Research; Rats; Rats, Wistar; Recombinant Fusion Proteins - genetics; Recombinant Fusion Proteins - metabolism; Secretory Vesicles - metabolism; Secretory Vesicles - ultrastructure; Staining and Labeling; Transfection; Neuropeptide Y; Myosin Va; Hippocampal neurons; Large dense core vesicles; Axonal transport
• ISSN: 0272-4340; 1573-6830
• DOI: 10.1007/s10571-009-9459-2

Axonal transport of peptide and hormone-containing large dense core vesicles (LDCVs) is known to be a microtubule-dependent process. Here, we suggest a role for the actin-based motor protein myosin Va specifically in retrograde axonal transport of LDCVs. Using live-cell imaging of transfected hippocampal neurons grown in culture, we measured the speed, transport direction, and the number of LDCVs that were labeled with ectopically expressed neuropeptide Y fused to EGFP. Upon expression of a dominant-negative tail construct of myosin Va, a general reduction of movement in both dendrites and axons was observed. In axons, it was particularly interesting that the retrograde speed of LDCVs was significantly impaired, although anterograde transport remained unchanged. Moreover, particles labeled with the dominant-negative construct often moved in the retrograde direction but rarely in the anterograde direction. We suggest a model where myosin Va acts as an actin-dependent vesicle motor that facilitates retrograde axonal transport.