Dynamic behavior and organization of cytoskeletal proteins in neurons: reconciling old and new findings

Neurofilament Transport Is Dependent on Actin and Myosin

“…Axonal transport is divided into two broad categories termed "slow" and "fast" axonal transport (for review, see Hirokawa, 1993;Nixon, 1998;Brady, 2000;Gallant, 2000). The way in which neurons achieve these varying transport rates has been postulated to arise either from using motor complexes that translocate at different speeds (for review, see Hirokawa, 1998;Brady, 2000) or by varying the duration of association of cargo with a single transport system (Ochs, 1975).…”

“…Any NF subunits associated with such moving microtubules therefore also would be propelled in an anterograde direction by dynein-mediated microtubule transport (Susalka and Pfister, 2000). Association of NFs with microtubules, including such moving microtubules, could be mediated either by direct association (Miyasaka et al, 1993;Shah et al, 2000) or linkage via additional microtubule motor proteins (Liao and Gundersen, 1998;Shah et al, 2000), other microtubule-associated proteins (Miyata et al, 1986;Hirokawa et al, 1988), and/or NF-associated proteins such as plectins (Nixon, 1998;Yang et al, 1999;Herrmann and Aebi, 2000). Notably, this line of reasoning encompasses the concept that kinesin may serve to link NF subunits with microtubules (Liao and Gundersen, 1998) in addition to (or instead of) actively translocating microtubules (Yabe et al, 1999.…”

“…In this regard, dynein transports NFs along microtubules under cell-free conditions (Shah et al, 2000). The ability of fast axonal transport motors such as kinesin and dynein to translocate NF subunits despite their overall translocation at a rate consistent with slow transport (Nixon, 1992(Nixon, , 1998Hirokawa, 1993;Galbraith and Gallant, 2000;Shea, 2000) is explained by the observation that NFs undergo short bursts of rapid transport that are interrupted by prolonged pauses (Roy et al, 2000;Wang et al, 2000;Ackerley et al, 2003).…”

Extreme Stretch Growth of Integrated Axons

“…The rapid and sustained stretch growth demonstrated here clearly shows that the physiological capacity of axons to rapidly and continuously expand is not limited by protein synthesis, transport rates, or the availability of structural constituents (Lamoureux et al, 1998;Alvarez et al, 2000;Brown, 2000;Roy et al, 2000;Brittis et al, 2002). Because of the increased demand to add structure during stretch growth, an alternative axon growth process such as intercalated addition of the membrane and cytoskeleton may occur, as has previously been suggested (Khanin et al, 1998;Nixon, 1998c). Although the cellular processes of extreme stretch growth have yet to be elucidated, the current data demonstrate that an initiating mechanism is mechanical transduction.…”

Neurofilament Polymer Transport in Axons

“…Cytoskeletal and cytosolic proteins move along axons in the slow components of axonal transport, but the mechanism of movement is not well understood and has been debated for almost three decades (Baas and Brown, 1997;Hirokawa et al, 1997;Nixon, 1998;Shah and Cleveland, 2002). Recent studies on the movement of green fluorescent protein (GFP)-tagged neurofilament proteins in cultured neurons have demonstrated that these proteins actually move at fast rates and that the movements are also intermittent and bidirectional (Yabe et al, 1999;Roy et al, 2000;Wang et al, 2000;Wang and Brown, 2001;Helfand et al, 2003).…”