Q. Wei et al., THE PREDOMINANT DEFECT IN DILUTE MELANOCYTES IS IN MELANOSOME DISTRIBUTION AND NOT CELL-SHAPE, SUPPORTING A ROLE FOR MYOSIN-V IN MELANOSOMETRANSPORT, Journal of muscle research and cell motility, 18(5), 1997, pp. 517-527
Mice with mutations at the dilute locus, which encodes the heavy chain
of a type V unconventional myosin, exhibit a reduction in coat colour
intensity. This defect is thought to be caused by the absence in dilu
te melanocytes of the extensive dendritic arbor through which these se
lls normally deliver pigment-laden melanosomes to keratinocytes. The d
ata on which this conclusion has been based can also be explained, how
ever, by a defect in the outward transport of melanosomes within melan
ocytes of normal shape. To resolve this question, we compared the shap
e and pigment distribution within melanocytes present in primary cultu
res prepared from the epidermis of C57BL/6J pups that were either wild
type (D/D) at dilute or homozygous for the dilute null allele d(120J)
. These same comparisons were also performed on melanocytes in situ, w
here antibodies to the membrane tyrosine kinase receptor cKIT were use
d to visualize melanocyte cell shape independent of pigment distributi
on. Wild type melanocytes were found to be dendritic and to have melan
osomes distributed throughout their dendrites both in vitro and in sit
u. Mutant melanocytes were also found to be dendritic in both cases, b
ut their melanosomes were highly concentrated in the cell body and lar
gely excluded from dendrites. We conclude, therefore, that the predomi
nant defect in dilute melanocytes is in melanosome distribution, not c
ell shape. These results argue that the myosin V isoform Encoded by th
e dilute locus functions in dendritic extensions to move melanosomes f
rom their site of formation within the cell body to their site of inte
rcellular transfer at dendritic tips. This conclusion is consistent wi
th our recent demonstration by immunolocalization that the dilute myos
in V isoform associates with melanosomes in mouse melanocytes.