Dj. Sharp et al., TRANSPORT OF DENDRITIC MICROTUBULES ESTABLISHES THEIR NONUNIFORM POLARITY ORIENTATION, The Journal of cell biology, 130(1), 1995, pp. 93-103
The immature processes that give rise to both axons and dendrites cont
ain microtubules (MTs) that are uniformly oriented with their plus-end
s distal to the cell body, and this pattern is preserved in the develo
ping axon. In contrast, developing dendrites gradually acquire nonunif
orm MT polarity orientation due to the addition of a subpopulation of
oppositely oriented MTs (Baas, P. W., M. M. Black, and G. A. Banker. 1
989. J. Cell Biol. 109:3085-3094). In theory, these minus-end-distal M
Ts could be locally nucleated and assembled within the dendrite itself
, or could be transported into the dendrite after their nucleation wit
hin the cell body. To distinguish between these possibilities, we expo
sed cultured hippocampal neurons to nanomolar levels of vinblastine af
ter one of the immature processes had developed into the axon but befo
re the others had become dendrites. At these levels, vinblastine acts
as a kinetic stabilizer of MTs, inhibiting further assembly while not
substantially depolymerizing existing MTs. This treatment did not abol
ish dendritic differentiation, which occurred in timely fashion over t
he next two to three days. The resulting dendrites were flatter and sh
orter than controls, but were identifiable by their ultrastructure, ch
emical composition, and thickened tapering morphology. The growth of t
hese dendrites was accompanied by a diminution of MTs from the cell bo
dy, indicating a net transfer of MTs from one compartment into the oth
er. During this time, minus-end-distal microtubules arose in the exper
imental dendrites, indicating that new MT assembly is not required for
the acquisition of nonuniform MT polarity orientation in the dendrite
. Minus-end-distal microtubules predominated in the more proximal regi
on of experimental dendrites, indicating that most of the MTs at this
stage of development are transported into the dendrite with their minu
s-ends leading. These observations indicate that transport of MTs from
the cell body is an essential feature of dendritic development, and t
hat this transport establishes the nonuniform polarity orientation of
MTs in the dendrite.