Figure 7.

Model of neurofilament-dependent structuring of axoplasm. Axoplasm is organized into a volume-determining three-dimensional array by a series of linkages that span between adjacent neurofilaments (blue-gray) and between neurofilaments and microtubules (red) or cortical actin (blue) filaments. The NF-M tail (turquoise) sets nearest neighbor spacing of neurofilaments, possibly dependent on phosphorylation of its KSP repeats. (The interaction is drawn here between NF-M tails bound to adjacent neurofilaments, although the alternative of the tail directly contacting the adjacent filament core is equally plausible; see also Nakagawa et al. [1995].) NF-H (purple) normally also crossbridges neurofilaments to each other (Hirokawa et al., 1984), but this is not necessary for establishing nearest neighbor spacing. NF-H may also contribute to a three-dimensional array by crossbridging between neurofilaments and microtubules. Other interfilament linkages are provided by plectin (orange), which is capable of bridging between neurofilaments and cortical actin filaments (blue) and neurofilaments and microtubules (Wiche, 1989; Errante et al., 1994; Svitkina et al., 1996). Final structural stability is contributed by the BPAG1n/dystonin family of cross-linkers that in motor and sensory axons (Dowling et al., 1997; Dalpe et al., 1998) provide additional linkage between neurofilaments and actin filaments (Yang et al., 1996) that are tethered under the cortical membrane. In the absence of NF-H, cross-linking from NF-M, plectin, and BPAG1n/dystonin homologues continue to support a three-dimensional array necessary for acquisition and maintenance of normal axonal volume.