Myosin va mediates docking of secretory granules at the plasma membrane
J Neurosci. 2007-09-26; 27(39): 10636-45
DOI: 27/39/10636 [pii]10.1523/JNEUROSCI.1228-07.2007
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Myosin Va (MyoVa) is a prime candidate for controlling actin-based organelle
motion in neurons and neuroendocrine cells. Its function in secretory granule
(SG) trafficking was investigated in enterochromaffin cells by wide-field and
total internal reflection fluorescence microscopy. The distribution of endogenous
MyoVa partially overlapped with SGs and microtubules. Impairing MyoVa function by
means of a truncated construct (MyoVa tail) or RNA interference prevented the
formation of SG-rich regions at the cell periphery and reduced SG density in the
subplasmalemmal region. Individual SG trajectories were tracked to analyze SG
mobility. A wide distribution of their diffusion coefficient, D(xy), was
observed. Almost immobile SGs (D(xy) < 5 x 10(-4) microm2 x s(-1)) were
considered as docked at the plasma membrane based on two properties: (1) SGs that
undergo exocytosis have a D(xy) below this threshold value for at least 2 s
before fusion; (2) a negative autocorrelation of the vertical motion was found in
subtrajectories with a D(xy) below the threshold. Using this criterion of
docking, we found that the main effect of MyoVa inhibition was to reduce the
number of docked granules, leading to reduced secretory responses. Surprisingly,
this reduction was not attributable to a decreased transport of SGs toward
release sites. In contrast, MyoVa silencing reduced the occurrence of
long-lasting, but not short-lasting, docking periods. We thus propose that,
despite its known motor activity, MyoVa directly mediates stable attachment of
SGs at the plasma membrane.
DOI: 10.1523/JNEUROSCI.1228-07.2007
PMID: 17898234 [Indexed for MEDLINE]