MAP2 and tau bind longitudinally along the outer ridges of microtubule protofilaments

Abstract

MAP2 and tau exhibit microtubule-stabilizing activities that are implicated in the development and maintenance of neuronal axons and dendrites. The proteins share a homologous COOH-terminal domain, composed of three or four microtubule binding repeats separated by inter-repeats (IRs). To investigate how MAP2 and tau stabilize microtubules, we calculated 3D maps of microtubules fully decorated with MAP2c or tau using cryo-EM and helical image analysis. Comparing these maps with an undecorated microtubule map revealed additional densities along protofilament ridges on the microtubule exterior, indicating that MAP2c and tau form an ordered structure when they bind microtubules. Localization of undecagold attached to the second IR of MAP2c showed that IRs also lie along the ridges, not between protofilaments. The densities attributable to the microtubule-associated proteins lie in close proximity to helices 11 and 12 and the COOH terminus of tubulin. Our data further suggest that the evolutionarily maintained differences observed in the repeat domain may be important for the specific targeting of different repeats to either α or β tubulin. These results provide strong evidence suggesting that MAP2c and tau stabilize microtubules by binding along individual protofilaments, possibly by bridging the tubulin interfaces.

Intracellular transport driven by cytoskeletal motors: General mechanisms and defects

“…Moreover the density of motors should be low since itions in open tube systems ingle motors or, equivalently, ting motors, we have obtained the cases of a single filament or three-dimensional space, as , these random walks exhibit average position of the motor with time. The same drift bement along a single filament ments with the same dimenaccessible to experiment [9]. nt a detailed derivation of the ] for movements in two and ning boundaries.…”

“…Either there is a -yet not fully specifiedmechanism that coordinates the motion of motors, so that motors of one type are inhibited while the others pull the cargo and the other way round, or bidirectional motion emerges spontaneously through stochastic fluctuations of the number of motors attached on the cargo at a given time. The latter mechanism is referred to as "tug-of-war" 9 .…”

“…2). The latter parameter is needed for modeling realistic situations, in which the diffusion coefficient in the fluid is much larger than on the filament [9]. The ordinary random walk in two dimensions has ␥ = 0, ␦ = 1 / 2, and ⑀ = 1.…”

“…The MT binding domain is able to bind at the outside of the MT cylinder as well as across protofilaments [9,320]. The interactions between the hydrophobic parts of MAPs induce constraints on the structure of MTs (see Fig.…”

Transitions in microtubule C-termini conformations as a possible dendritic signaling phenomenon

“…Indeed MAP2 binds to helices 11 and 12 near the C-termini of tubulin in MTs (Al-Bassam et al, 2002). While precise nature of the bond is not known at present, it is suspected to be ionic due to oppositely charged regions of tubulin and MAP2 in the binidng areas.…”