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News Physiol Sci 14: 175, 1999;
1548-9213/99 $5.00
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News in Physiological Sciences, Vol. 14, No. 4, 175, August 1999
© 1999 Int. Union Physiol. Sci./Am. Physiol. Soc.

Trendsetters

ER Muscles Its Way Around Neurons

George M. Langford

Department of Biological Sciences Dartmouth College Hanover, NH 03755-3576
In this section we feature some of the latest and most striking new findings in physiology, interpreting the term "physiology" in its broadest sense. In each instance, an effort will be made to place the new findings in perspective.

Heinz Valtin

Editor, TRENDSETTERS

In neuronal cells, smooth endoplasmic reticulum (SER) is a key component of the neuronal signaling process. SER is distributed throughout neurons, and it represents the principal site for the storage and release of the intracellular second messenger, calcium. As the primary site of Ca2+ release, as well as of Ca2+ uptake, the SER regulates the local cytosolic Ca2+ concentration and hence the coupling of electrical excitation to the activation of signal transduction cascades. To perform these functions, the SER must be positioned at the proper location within the cell, which, in the case of neurons, is the dendritic spines (Fig. 1Go), the sites of synaptic input to postsynaptic neurons. For example, in the dendritic spines of cerebellar Purkinje cells, excitation leads to Ca2+ influx through voltage-sensitive Ca2+ channels. This small influx triggers Ca2+-induced release of calcium from the SER via ryanodine receptors. In addition, excitation via metabotropic glutamate receptors leads to the production of inositol 1,4,5-trisphosphate (IP3), which causes the release of Ca2+ from the SER through IP3 receptors. By these mechanisms, Ca2+ is thought to initiate the cellular mechanisms that lead—among other functions—to learning and memory appropriate to the neuron in question.



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  		FIGURE 1. Transport of smooth endoplasmic reticulum (ER) vesicles from the dendritic shaft into the dendritic spine of a cerebellar Purkinje cell. Details are described in the text.

 
The mechanism by which SER is transported through the slender neck at the base of dendritic spines and retained within the spine proper is not known, but recent studies (3) provide clues to the answer. By means of videomicroscopy on the giant squid axon, Tabb et al. (3) showed that SER vesicles (SER cisternae) are transported on actin filaments. Function-blocking antibodies specific for myosin V were used to demonstrate that myosin V is the motor for SER transport on actin filaments. Kinesin was also identified on the SER vesicles (3), and this association allows SER transport on microtubules. The identification of myosin V and kinesin on SER vesicles is interpreted to suggest that movement of these vesicles occurs on microtubules in the dendritic shafts and on actin filaments into the dendritic spines—and that there is, therefore, a switch of the vesicles from one track to the other.

If this view is correct, coordination between the microtubule-dependent motor (kinesin) and the actin-dependent motor (myosin V) is needed to deliver SER vesicles to their site of action in the dendritic spines. Recent evidence suggests, in fact, that there is a direct interaction between kinesin and myosin V (1). Huang and his collaborators (1) used the yeast two-hybrid assay to show that the tail domain of myosin V and the rod-tail domain of kinesin bind to each other. The fragments of myosin V that interacted with the distal rod domain of the kinesin heavy chain were those that spanned the AF-6/cno homology domain of the myosin globular tail. In addition to these results with the two-hybrid assay, Huang et al. expressed myosin V constructs in bacteria and showed that the tail fragments of myosin V, which contain the AF-6/cno homology domain, coimmunoprecipitated with the heavy chain of kinesin in mouse brain extracts. Thus the direct interaction of the tail domains of these two motors has been established, and it may hold a key to the mechanism by which the transport of SER vesicles on microtubules and actin filaments is coordinated.

These data provide further support for the vesicle-transport model in neurons, in which long-range transport occurs on microtubules and short-range transport occurs on actin filaments (2). The next step is to determine the mechanism by which the shift from microtubules to actin filaments and the concomitant shift from kinesin to myosin V occur.

References

  1. Huang, J.-D., S. T. Brady, B. W. Richards, D. Stenoien, H. H. Resau, N. G. Copeland, and N. A. Jenkins. Direct interaction of microtubule- and actin-based transport motors. Nature 397: 267–270, 1999.[Medline]
  2. Langford, G. M., and B. J. Molyneaux. Myosin-V in the brain: mutations lead to neurological defects. Brain Res. Rev. 28: 1–8, 1998.
  3. Tabb, J. S., B. J. Molyneaux, D. L. Cohen, S. A. Kuznetsov, and G. M. Langford. Transport of ER vesicles on actin filaments in neurons by myosin-V. J. Cell Sci. 111: 3221–3234, 1998.[Abstract]

Occasionally, the Editor of the Trendsetters section invites contributions from the authors of published scientific articles that have been identified as being of special interest. All précis to Trendsetters are by invitation only.




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