The Light Chain 1 Subunit of the Microtubule-Associated Protein 1B (MAP1B) Is Responsible for Tiam1 Binding and Rac1 Activation in Neuronal Cells

Abstract

Microtubule-associated protein 1B (MAP1B) is a neuronal protein involved in the stabilization of microtubules both in the axon and somatodendritic compartments. Acute, genetic inactivation of MAP1B leads to delayed axonal outgrowth, most likely due to changes in the post-translational modification of tubulin subunits, which enhances microtubule polymerization. Furthermore, MAP1B deficiency is accompanied by abnormal actin microfilament polymerization and dramatic changes in the activity of small GTPases controlling the actin cytoskeleton. In this work, we showed that MAP1B interacts with a guanine exchange factor, termed Tiam1, which specifically activates Rac1. These proteins co-segregated in neurons, and interact in both heterologous expression systems and primary neurons. We dissected the molecular domains involved in the MAP1B-Tiam1 interaction, and demonstrated that pleckstrin homology (PH) domains in Tiam1 are responsible for MAP1B binding. Interestingly, only the light chain 1 (LC1) of MAP1B was able to interact with Tiam1. Moreover, it was able to increase the activity of the small GTPase, Rac1. These results suggest that the interaction between Tiam1 and MAP1B, is produced by the binding of LC1 with PH domains in Tiam1. The formation of such a complex impacts on the activation levels of Rac1 confirming a novel function of MAP1B related with the control of small GTPases. These results also support the idea of cross-talk between cytoskeleton compartments inside neuronal cells.

Nerve growth factor promotes reorganization of the axonal microtubule array at sites of axon collateral branching

“…This correlation suggests that the decreased levels of MAP1B on microtubules during the early phases of branch formation may serve to prevent the entry of mitochondria into branches that have not yet sufficiently matured by promoting their retrograde movement. MAP1B can also positively regulate Rac1 activity through regulation of the TIAM1 GEF (Montenegro‐Venegas et al, ; Henriquez et al, ). Rac1 is involved in the formation of branches along sensory axons through the positive regulation of WAVE1‐mediated activation of the Arp2/3 actin nucleation complex, which drives the formation of the axonal actin patches from which filopodia emerge (Spillane et al, ).…”

Actin filaments and microtubules in dendritic spines

“…Interestingly, MAP1B binds to Tiam1, a guanine exchanging factor that promotes Rac1 activity (Henríquez et al . ).…”

The MAP1B case: An old MAP that is new again

“…LC1 binds to the GEFs for Rac1, STEF, and TIAM1 (Takefuji et al, ; Henriquez et al, ), enhancing TIAM1 GEF activity, which is relevant during axonal growth and synaptic plasticity, as TIAM1 overexpression can rescue MAP1B KO mice phenotypes during both processes (Montenegro‐Venegas et al, ; Benoist et al, ).…”