The discovery of Kinesin-1 stemmed directly from real-time observation of fast axonal transport in isolated squid axoplasm by video-enhanced light microscopy. The non-hydrolyzable ATP analog, AMP-PNP, was found to inhibit fast axonal transport and to promote tight binding of organelles to microtubules. This key observation suggested that AMP-PNP induces the formation of rigor complexes consisting of organelles, microtubules and microtubule motor proteins [7]. To identify the putative motor, taxol-stabilized microtubules were isolated from squid optic lobes or vertebrate brain in the presence or absence of AMP-PNP. Analysis of the microtubules by SDS-PAGE revealed an ~120 kDa polypeptide that bound to microtubules in an AMP-PNP-dependent manner. The ATPase activity of the AMP-PNP microtubules was much higher than that of the control microtubules [4]. Moreover, a multisubunit enzyme containing the ~120 kDa polypeptide was purified and when adsorbed to glass coverslips, promoted ATP-dependent gliding of microtubules. Based on its mechanochemical activity, the ability to induce ATP-dependent microtubule gliding, the protein was aptly named kinesin (recently renamed Kinesin-1) [5,8]. Further studies have led to the discovery of a large number of proteins that are related in structure to Kinesin-1 and constititute the kinesin superfamily of motor proteins. These proteins are found in organisms representing all of the major eukaryotic kingdoms. The common bond among the kinesins is a highly conserved ‘motor’ domain, ~350 amino acids long, which contains binding sites for ATP and microtubules. The kinesin proteins are presumed to function in vivo as motors for microtubule-dependent motile phenomena, such as membrane transport and chromosome movement during meiosis and mitosis. Contributed by George S. Bloom Literature Cited Return to the Kinesin Home Page.
Until the mid-1980’s, motor proteins that worked in concert with cytoplasmic microtubules represented a class of molecules whose identification remained a mystery. The existence of microtubule motors had been inferred from analysis of chromosome segregation and spindle dynamics during mitosis and meiosis, and of transport through the cytoplasm of membrane-bounded organelles. Numerous studies indicated that these motile phenomena required both microtubules and ATP, suggesting that mechanochemical ATPases were responsible for moving a variety of intracellular cargo along cytoplasmic microtubules. For many years the leading candidate ATPase was dynein, which had been known since the 1960’s to be a motor for ciliary and flagellar motility [1]. Periodic reports of cytoplasmic dyneins emerged over the ensuing years, but the first definitive evidence that such proteins existed was not published until 1987 [2, 3]. The discovery of cytoplasmic dynein represented a landmark in cell biology, but occured two years after publication of an equally momentous event, the discovery of the novel microtubule motor protein, Kinesin-1 (formerly known as kinesin, conventional kinesin or KHC) [4-6].
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Created 22 July 1996 16:00 GMT
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