Myosin Va facilitates the distribution of secretory granules in the F-actin rich cortex of PC12 cells.
Neuroendocrine secretory granules, the storage organelles for neuropeptides and hormones, are formed at the trans-Golgi network, stored inside the cell and exocytosed upon stimulation. Previously, we have reported that newly formed secretory granules of PC12 cells are transported in a microtubule-dependent manner from the trans-Golgi network to the F-actin-rich cell cortex, where they undergo short directed movements and exhibit a homogeneous distribution. Here we provide morphological and biochemical evidence that myosin Va is associated with secretory granules. Expression of a dominant-negative tail domain of myosin Va in PC12 cells led to an extensive clustering of secretory granules close to the cell periphery, a loss of their cortical restriction and a strong reduction in their motility in the actin cortex. Based on this data we propose a model that implies a dual transport system for secretory granules: after microtubule-dependent delivery to the cell periphery, secretory granules exhibit a myosin Va-dependent transport leading to their restriction and even dispersal in the F-actin-rich cortex of PC12 cells.
Rudolf
Rüdiger
R
Department of Neurobiology, Interdisciplinary Center of Neuroscience, University of Heidelberg, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany.
Kögel
Tanja
T
Kuznetsov
Sergei A
SA
Salm
Thorsten
T
Schlicker
Oliver
O
Hellwig
Andrea
A
Hammer
John A
JA
Gerdes
Hans-Hermann
HH
D000199:Actins / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002451:Cell Compartmentation / Q000502:physiology; D003593:Cytoplasm / Q000378:metabolism* / Q000648:ultrastructure; D003599:Cytoskeleton / Q000378:metabolism* / Q000648:ultrastructure; D008854:Microscopy, Electron; D008870:Microtubules / Q000378:metabolism / Q000648:ultrastructure; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D024701:Myosin Type V / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D016716:PC12 Cells; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism* / Q000648:ultrastructure
D000199:Actins; C513081:Myo5a protein, rat; D024701:Myosin Type V; D018995:Myosin Heavy Chains