Differential expression of distinct microtubule-associated proteins during brain development.

Abstract

The levels of three different microtubuleassociated proteins (MAP1, -2, and -3) in brain were found to undergo large changes during postnatal development. MAPi was barely detectable at birth but thereafter steadily increased, reaching adult levels by postnatal day 20 (P20). Both MAP2 and MAP3 showed differential expression patterns of their component peptides. At birth, MAP2 was represented by the smaller of two Mr 280,000 peptides (MAP2b) and three antigenically related Mr 70,000 peptides. The larger of the M, 280,000 peptides (MAP2a) first appeared between P10 and P20, and the Mr 70,000 components disappeared at the same time. Of the two MAP3 peptides, the larger (MAP3a) was present in the late embryo, several days before MAP3b appeared. Between P10 and P20, both MAP3 components underwent a striking decrease in abundance (a factor of 10), which correlated with their disappearance from all neuronal compartments except neurofrlament-containing axons. These developmental changes in expression are different and characteristic for each of the three MAPs, yet in each case they are detectable in brain homogenates, indicating that they occur concurrently throughout the brain.The assembly of microtubules is an essential step in the growth of neuronal processes (1-3). Although very little is known about its regulation in the developing nervous system, it is believed that microtubule-associated proteins (MAPs) are involved (4-9). Three MAP species have been shown by immunohistochemistry to be differentially distributed in the brain, differing both in the types of cells in which they occur and in their distribution within the neuronal cytoplasm (10). MAPi is, according to our observations, associated exclusively with neurons in the adult brain and is more abundant in dendrites than in axons (11-13). MAP2 is also neuron specific and is predominantly, and probably exclusively, located in dendrites (12, 14-18). MAP3 occurs in both neurons and glia, but in neurons it is restricted to neurofilament-rich axons (10,19). In a recent immunohistochemical study, we followed the appearance of these proteins in the developing rat cerebellum and found that each exhibits a characteristic developmental pattern (26). MAPi appears in axons before dendrites, but the balance changes during the first 3 postnatal weeks by the gradual accumulation of MAPi in dendrites and by its simultaneous decrease in axons. MAP2 is exclusively associated with dendrites throughout development. MAP3 appears transitorily in nascent axons (from which it is absent in mature tissue) and later appears in glial cell bodies and processes.These changes in cellular distribution indicate that the expression of these proteins is developmentally regulated. In the present study, we have used monoclonal antibodies to trace the appearance of MAPi, -2, and -3 in rat brain from the late embryo to the end of the third postnatal week. We find that each MAP shows a distinct developmental pattern, which includes large changes in the abundance of their components that occ...

Expression of neuron-specific tubulin defines a novel population in the proliferative layers of the developing telencephalon

“…This molecule has been shown to be present in postmigratory, differentiating neurons, and first appears in cells of the subplate and marginal zones before being detected in the later generated cortical plate (Crandall et al, 1986;Chun and Shatz, 1989). As MAP2 belongs to a family of developmentally regulated isoforms (Johnson and Jope, 1992) we have used two antibodies that are known to recognize all isoforms of this molecule (MAP2-3, Chun and Shatz, 1989;HM2, Tucker et al, 1988) and in particular the embryonic low-molecular-weight form, MAP2c, which is expressed earlier than other forms (Riederer and Matus, 1985).…”

Induction of axon and dendrite formation during early RGC-5 cell differentiation

“…MAP2 exists in several isoforms, the most prevalent of which are MAP2a, b and c. MAP2a and b are present in dendrites of mature neurons (Bernhardt and Matus, 1984;Matus et al, 1981). MAP2c is a smaller splice variant and is present in developing neurites (Meichsner et al, 1993), including axons of developing RGCs (Tucker and Matus, 1988), but is absent in mature neurons (Riederer and Matus, 1985). Previous studies have shown that expression of MAP2 is necessary for retinoic acid-induced differentiation of embryonal carcinoma cells (Dinsmore and Solomon, 1991), and that specific expression of MAP2c is sufficient to induce microtubule reorganization in a neuronal cell line and initiate neurite outgrowth (Dehmelt et al, 2003).…”

Tubulin-Mediated Binding of Human Immunodeficiency Virus-1 Tat to the Cytoskeleton Causes Proteasomal-Dependent Degradation of Microtubule-Associated Protein 2 and Neuronal Damage

“…The best studied MAPs in the nervous system are MAP2, mostly localized in the dendrites, and Tau, more abundant in axons (Binder et al, 1985;Riederer and Matus, 1985). MAP2 activity is critical for microtubule nucleation, polymerization, stability, and bundling (Chen et al, 1992;Ferralli et al, 1994), as well as microtubular transport (Lopez and Sheetz, 1995;Sato-Harada et al, 1996).…”