Polarity orientation of microtubules in hippocampal neurons: uniformity in the axon and nonuniformity in the dendrite.

Abstract

We have analyzed the polarity orientation of microtubules in the axons and dendrites of cultured rat hippocampal neurons. As previously reported of axons from other neurons, microtubules in these axons are uniform with respect to polarity; (+)-ends are directed away from the cell body toward the growth cone. In sharp contrast, microtubules in the mid-region of the dendrite, -75 Jtm from the cell body, are not of uniform polarity orientation. Roughly equal proportions of these microtubules are oriented with (+)-ends directed toward the growth cone and ( + )-ends directed .toward the cell body. At distances within 15 ,um of the growth cone, however, microtubule polarity orientation in dendrites is similar to that in axons; (+)-ends are uniformly directed toward the growth cone. These findings indicate a clear difference between axons and dendrites with respect to microtubule organization, a difference that may underlie the differential distribution of organelles within the neuron.Vertebrate neurons generate and maintain two morphologically and functionally distinct types of neurites, axons and dendrites (1-6). It has long been recognized that axons and dendrites differ in their complements of cytoplasmic organelles (1, 6). Most notable in this regard, ribosomes and Golgi elements are present in dendrites but are absent from axons. What is the basis for the nonuniform distribution of organelles in neurons? Several lines of evidence indicate that the distribution of organelles in a cell reflects active transport processes that selectively convey organelles from their sites of synthesis and assembly to other locations in the cell (7, 8).These observations raise the possibility that many of the differences between the organelle composition of axons and dendrites are produced by differences in the organization of the transport systems that convey materials from the cell body into the axon or dendrite.The transport of organelles is a microtubule-based process; microtubules provide the substrate for organelle translocation and, by virtue of their intrinsic polarity, influence the directionality of transport (7-9). The intrinsic polarity of microtubules is based on the asymmetry of the tubulin subunit and its self-assembly characteristics; the (+)-end is preferred for subunit addition over the (-)-end (10, 11). Microtubule-based translocators convey organelles specifically toward either the ( + )-or the ( -)-end ofthe microtubule (7-9). In the axon, microtubules are uniform with respect to polarity, with the (+ )-ends directed away from the cell body (12-15). Thus, only those organelles that translocate toward (+ )-ends of microtubules will be conveyed from the cell body into the axon.Do microtubules in dendrites have the same polarity orientation as those in axons? To date, information concerning the polarity orientation of dendritic microtubules derives from a few atypical cell types. In the dendrite-like processes of teleost retinal cone cells (16) and frog primary olfactory neurons (17), microtubules are unifo...

Generation of noncentrosomal microtubule arrays

“…In axons, MTs are generally long and uniformly oriented, their plus ends distal to the cell body, whereas in dendrites MTs are much shorter and exhibit mixed polarity ( Fig. 1) (Baas et al, 1989;Baas et al, 1988;Baas et al, 1991;Burton and Paige, 1981;Heidemann et al, 1981). In neither case are MTs attached to the centrosome or any known nucleating structure.…”

Tau protein: An update on structure and function

“…Besides this difference in microtubule-associated proteins, a difference in the polarity of the microtubules in the axon and the dendrites also exists. Baas et al [1988] have found that dendrites contain microtubules with equal numbers oriented plus ends toward the growth cone and plus ends toward the cell body; axonal microtubules are uniformly oriented with all plus ends toward the growth cone. The relationship between this organization of axonal and dendritic microtubules and their associated proteins has yet to be shown, Major questions to be answered are 1) What mechanism(s) results in the localization of tau to the axon and MAP2 to the dendrite?…”

How does an axon grow?

“…For example, microtubules in axons and dendrites point in opposite directions-in axons, the microtubules all have their plus ends pointed away from the cell body; in dendrites, microtubules are oriented in both directions. Initially, however, the undifferentiated neurites all have plus-end-distal axonlike microtubules; minus-end-distal microtubules are steadily added to dendrites on neurite differentiation (Baas et al 1988(Baas et al , 1989. A microtubule motor protein, CHO1/MKLP1, is responsible for this later minus-enddistal transport, and subsequent differentiation such as the dendritic predominance of golgi and ribosomes discussed above is also lost if CHO1/MKLP1 is depleted (Yu et al 2000).…”