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It has recently been reported that high molecular weight microtubule-associated proteins are differently distributed in dendrites and axons of neurons [ Matus Bernhardt and Hugh-Jones (1981), Proc. natn Acad. Sci. U.S.A. 78, 3010-3014; Vallee (1982), J. Cell Biol. 92, 435-442]. We have reported earlier in a preliminary form [Miller, Walter, Theurkauf , Vallee and De Camilli (1982), Proc. natn Acad. Sci. U.S.A. 79, 5562-5566] that an antiserum specific for microtubule-associated protein 2, one of the most prominent high molecular weight microtubule-associated proteins in brain and a major brain phosphoprotein, stains specifically neuronal dendrites and perikarya. We have now extended those observations by performing a detailed analysis of the distribution of microtubule-associated protein 2 throughout the nervous system of the rat. We found that microtubule-associated protein 2 is present at high concentrations in the great majority of neurons. Under our conditions of immunostaining microtubule-associated protein 2 was not detected in nonneuronal cells. In all neurons it was compartmentalized in perikarya and dendrites. In most cases, the latter were more heavily stained than perikarya. The pattern of staining (overall intensity, relative intensity in dendrites vs perikarya, and in proximal vs distal segments of the dendritic tree), varied in different classes of neurons but was identical for all neurons with similar geometry in the same brain region. Different patterns of staining were found in dendritic trees with dissimilar branching characteristics. In all cases staining for microtubule-associated protein 2 in dendrites was consistent with a localization of microtubule-associated protein 2 on dendritic microtubules. Neuronal processes clearly identifiable as axons or axon terminals were not immunostained. Afferent processes of primary sensory cells were also unstained. Our findings indicate that microtubule-associated protein 2 is a component of the vast majority, and possibly all, neurons. It is highly concentrated in "bona fide" dendrites, i.e. in processes specialized for the reception of synaptic inputs on their surface and highly dependent on such inputs for their growth. The location of microtubule-associated protein 2, a major target for second messenger-regulated protein kinases, in these processes, supports the hypothesis that its phosphorylation might participate in the transduction of neurotransmitter signals in target nerve cells.

Kinesins are microtubule-dependent molecular motors involved in intracellular transport and mitosis. Here, we report the cloning, sequencing, mapping, and expression of a novel member of the kinesin superfamily. The sequence of this newly identified human cDNA reveals an open reading frame encoding a putative protein of 792 residues. Based on its high sequence similarity to the kinesin-like molecule KIF3B, we named this protein KIF3C. KIF3C is encoded by transcripts that are distinct from the KIF3B mRNA in human, rat, and mouse and is preferentially expressed in the brain. Fluorescence in situ hybridization reveals that, in the human genome, the KIF3C gene maps to chromosome 2 at 2p23. The sequence of KIF3C predicts an unusually long insertion in the proximity of L11, a region thought to mediate microtubule binding. Taken together, these findings suggest that KIF3C is a novel kinesin-like protein that might be specifically involved in microtubule-based transport in neuronal cells.

1 The anti‐hypertensive effect of labetalol given twice or three times daily was evaluated in ambulant subjects with essential hypertension by recording blood pressure directly for 24 h before and after 15 d of labetalol administration (daily dose 600‐1800 mg). 2 Labetalol reduced 24 h systolic and diastolic blood pressures by about 20%. The reduction was evident throughout the whole 24 h period, although it was less marked during sleep. The hypotensive effect was similar when the drug was given twice or three times daily. 3 The 24 h heart rate was reduced during labetalol treatment. However, this effect was less marked than the hypotensive effect and was not present in all subjects. 4 There was a reduction in the standard deviations of blood pressure and heart rate values. However, in neither case was the coefficient of variation altered, indicating that labetalol did not have any significant effect on the shape of the 24 h blood pressure measurements. 1982 The British Pharmacological Society