Myosin Function In Dendritic Spines

Dendritic spines are unique compartments because they contain little, if any microtubules, but are rich in actin filaments. Organelles, such as smooth endo-plasmic reticulum and ribososmes, as well as a large number of proteins that form the postsynaptic density need to be transported into dendritic spines. There is considerable evidence that these compartments undergo structural changes that are dependent upon actin filaments and neuronal activity40. Whether transport plays a role for such structural changes of spines is currently unknown. A number of studies report interactions of the myosins Va, Vb, and VI with synaptic proteins in dendritic spines. For instance, myosin Va binds indirectly to GKAP through an 8kDa protein originally identified as a dynein light chain41. Myosin Va further binds the synaptic protein CaMKII and contributes to its kinase activity42. The tail of myosin Vb was shown to indirectly interact with the M4 muscarinic acetylcholine receptor through Rab11a interactions43 and myosin VI binds to SAP97, a binding partner for the GluR1 subunit of AMPA-type glutamate receptors14. Functional evidence that myosin VI is important for dendritic spine structure comes from Snell's waltzer mice, deficient in the myosin VI protein. Hippocampi from these mice exhibit a decrease in synapse number and display abnormally short dendritic spines44. In addition, cultured hippocampal neurons from this genetic background display decreased numbers of both synapses and spines. Since myosin VI is an actin-based motor implicated in clathrin-mediated endocytosis in non-neuronal cells, it has been suggested that endocytosis of synaptic AMPA receptors might depend on myosin VI and the loss of endocytosis induces activity-dependent changes in synaptic structure44.


To generate and maintain cellular polarity with an axon and many dendrites, neurons use different cellular mechanisms. Both mRNAs and proteins are sorted and transported in protein-RNA complexes, organelles, or protein complexes, respectively. A number of motor proteins, specialized for transport of cargo material, recognize these complexes and recruit them over short or long distances within the cell. As the number of cargoes is generally much higher than the number of motors available for transport, specificity is required to recruit certain material to individual destinations. To address specificity, transport complexes not only consist of motor and cargo but also contain a variable number of adaptor or scaffolding proteins involved in motor-cargo attachment. Adaptor proteins also bind targeting signals within the polypeptide chain of cargo molecules that are thought to encode directionality of transport. Not all cargo molecules are selectively transported to their site of action. Polar cells also perform nonselective transport of material and eliminate cargo from inappropriate sites, for instance through endocytosis of transmembrane proteins. In this case, targeting signals might serve as recognition sites for the endocytic machinery to induce internalization of the respective proteins.

Molecular motors seem to be critical for all types of selective transport. Individual motors have a preference for either axons or dendrites, a phenomenon that is likely to be encoded by the molecular nature of the tracks along which motors move. Microtubule tracks are decorated by a variety of MAPs, most of which are target of post-translational modifications. Therefore, the interaction of individual motor-adaptor-cargo complexes, together with the individual nature of the tracks, generates a large combination of signals to encode directed delivery. Upon delivery of cargo at its final destination, interactions of cargo and adaptor/scaffolding proteins might remain to associate proteins for instance at subsynaptic membrane specializations such as the postsynaptic density.

Because of the large number of molecules to be transported, some transport mechanisms might be redundant. A more precise understanding of protein-protein interactions between tracks, motors, adaptors, and cargoes is required to distinguish between common principles and rather exceptional mechanisms of transport selectivity.


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