Cohen and pfaff microtubule-associated proteins (MAPs)and tau proteins. These proteins induce the assembly and stabilization of microtubules by binding to them. The tau proteins facilitate polymerization by bind ing to more than one tubulin dimer at the same time mAPs have two domains. one of which binds to the microtubule and the other to an adjacent MAP molecule, filament, or cell organelle. MAPs provide the neuron with a mechanism for struc tural plasticity and variability. About 10 kinds of MAPs have been identified, and they appear to be differentially expressed during brain development Specific MAPs appear to be restricted to different neuronal processes. MAP 2, for example, is expressed in dendrites but not axons(Fig. 7);con- versely, MAP 3 is present in axons but not in dendrites. Although microtubules appear in parallel array, actin filaments in neurons are usually visible as a tangled meshwork, The network sometimes appears as a dense submembranous array, as in the postsynaptic density(PSd) immediately beneath Fig6 Electron micrograph of the axonal cytoskeleton. The two the postsynaptic membrane. However, the network prominent cytoskeletal elements in this region are microtubules may be less dense, as in the subsynaptic web imme- (m)and neurofilaments(n). The microtubules are 25 nm in diately beneath the PSD and extending throughout diameter and form tracks for the transport of various orga- the dendritic spine. Actin filaments are also asso- nelles, such as vesicles(arrowheads ) The neurofilaments belong ciated with a group of accessory proteins, the may contribute to the resilience relatively stable polymers that actin-binding proteins, which bundle them or in diameter. Neurofilaments y and caliber of axons cross-link them to form a gel. Some binding pro- teins join the filament ends to obstruct further polymerization, and others link actin to the mem- control the rates of association and disassociation at brane. Actin-binding proteins are regulated the ends of each rod. In some polymers, there is a by second messengers, such as calcium or cyclic constant flux of monomers at each end. In more nucleotides stable polymers, dissociation of the subunits at each end is slow or does not occur at all. Stability can be 3. 2.3. MoLECULAR MOTORS achieved by blocking the dissociation reaction at Other proteins associated with the cytoskeleton either end. both tubulin and actin monomers are asymmetric so that they can only link up with each are the molecular motors, which harness energy to other in a specific orientation. Consequently, the propel themselves along filaments. These proteins are enzymes that hydrolyze ATP and GTP and use resultant polymer is polarized and has plus and the liberated energy to move themselves along the minus ends, a feature permitting polymers to grow in a directed manner polymer. Motion is achieved because each of the steps of nucleotide binding, hydrolysis, and release 3.2.2. CYTOSKELETAL-ASSOCIATED PROTEINS of ADP or gdp plus phosphate causes a concomi tant change in the conformation of the motor pro- Cytoskeletal-associated proteins regulate cyto- tein such that it is directed forward. Myosin skeletal structure and function and characterize spe- motors walk along actin filaments, which are cific neuronal domains. Purified tubulin monomers pulled along in the process. This action is impor- can spontaneously assemble into microtubules in tant in the motility of growth cones, the pioneering the presence of GTP. However, polymerization is tip of developing nerve cell processes. Motor pro greatly enhanced in impure preparations. The teins are also associated with microtubules. where impurities are actually a group of accessory pro- they are involved in organelle transport in neuro- teins that are subdivided into two categories: nal processescontrol the rates of association and disassociation at the ends of each rod. In some polymers, there is a constant flux of monomers at each end. In more stable polymers, dissociation of the subunits at each end is slow or does not occur at all. Stability can be achieved by blocking the dissociation reaction at either end. Both tubulin and actin monomers are asymmetric so that they can only link up with each other in a specific orientation. Consequently, the resultant polymer is polarized and has plus and minus ends, a feature permitting polymers to grow in a directed manner. 3.2.2. CYTOSKELETAL-ASSOCIATED PROTEINS Cytoskeletal-associated proteins regulate cyto￾skeletal structure and function and characterize spe￾cific neuronal domains. Purified tubulin monomers can spontaneously assemble into microtubules in the presence of GTP. However, polymerization is greatly enhanced in impure preparations. The impurities are actually a group of accessory pro￾teins that are subdivided into two categories: microtubule-associated proteins (MAPs) and tau proteins. These proteins induce the assembly and stabilization of microtubules by binding to them. The tau proteins facilitate polymerization by bind￾ing to more than one tubulin dimer at the same time. MAPs have two domains, one of which binds to the microtubule and the other to an adjacent MAP molecule, filament, or cell organelle. MAPs provide the neuron with a mechanism for struc￾tural plasticity and variability. About 10 kinds of MAPs have been identified, and they appear to be differentially expressed during brain development. Specific MAPs appear to be restricted to different neuronal processes. MAP 2, for example, is expressed in dendrites but not axons (Fig. 7); con￾versely, MAP 3 is present in axons but not in dendrites. Although microtubules appear in parallel array, actin filaments in neurons are usually visible as a tangled meshwork. The network sometimes appears as a dense submembranous array, as in the postsynaptic density (PSD) immediately beneath the postsynaptic membrane. However, the network may be less dense, as in the subsynaptic web imme￾diately beneath the PSD and extending throughout the dendritic spine. Actin filaments are also asso￾ciated with a group of accessory proteins, the actin-binding proteins, which bundle them or cross-link them to form a gel. Some binding pro￾teins join the filament ends to obstruct further polymerization, and others link actin to the mem￾brane. Actin-binding proteins are regulated by second messengers, such as calcium or cyclic nucleotides. 3.2.3. MOLECULAR MOTORS Other proteins associated with the cytoskeleton are the molecular motors, which harness energy to propel themselves along filaments. These proteins are enzymes that hydrolyze ATP and GTP and use the liberated energy to move themselves along the polymer. Motion is achieved because each of the steps of nucleotide binding, hydrolysis, and release of ADP or GDP plus phosphate causes a concomi￾tant change in the conformation of the motor pro￾tein such that it is directed forward. Myosin motors walk along actin filaments, which are pulled along in the process. This action is impor￾tant in the motility of growth cones, the pioneering tip of developing nerve cell processes. Motor pro￾teins are also associated with microtubules, where they are involved in organelle transport in neuro￾nal processes. Fig. 6. Electron micrograph of the axonal cytoskeleton. The two prominent cytoskeletal elements in this region are microtubules (m) and neurofilaments (n). The microtubules are 25 nm in diameter and form tracks for the transport of various orga￾nelles, such as vesicles (arrowheads). The neurofilaments belong to the ubiquitous class of intermediate filaments and are 10 nm in diameter. Neurofilaments are relatively stable polymers that may contribute to the resiliency and caliber of axons. 12 Cohen and Pfaff