Abstract
The development and function of the central nervous system rely on the microtubule (MT) and actin cytoskeletons and their respective effectors. Although the structural role of the cytoskeleton has long been acknowledged in neuronal morphology and activity, it was recently recognized to play the role of a signaling platform. Following this recognition, research into Microtubule Associated Proteins (MAPs) diversified. Indeed, historically, structural MAPs—including MAP1B, MAP2, Tau, and MAP6 (also known as STOP);—were identified and described as MT-binding and -stabilizing proteins. Extensive data obtained over the last 20 years indicated that these structural MAPs could also contribute to a variety of other molecular roles. Among multi-role MAPs, MAP6 provides a striking example illustrating the diverse molecular and cellular properties of MAPs and showing how their functional versatility contributes to the central nervous system. In this review, in addition to MAP6’s effect on microtubules, we describe its impact on the actin cytoskeleton, on neuroreceptor homeostasis, and its involvement in signaling pathways governing neuron development and maturation. We also discuss its roles in synaptic plasticity, brain connectivity, and cognitive abilities, as well as the potential relationships between the integrated brain functions of MAP6 and its molecular activities. In parallel, the Collapsin Response Mediator Proteins (CRMPs) are presented as examples of how other proteins, not initially identified as MAPs, fall into the broader MAP family. These proteins bind MTs as well as exhibiting molecular and cellular properties very similar to MAP6. Finally, we briefly summarize the multiple similarities between other classical structural MAPs and MAP6 or CRMPs.In summary, this review revisits the molecular properties and the cellular and neuronal roles of the classical MAPs, broadening our definition of what constitutes a MAP.
Highlights
Microtubule-Associated Proteins (MAPs) were discovered in the context of the study of microtubule (MT) stability in neurons during the 1970s (Weingarten et al, 1975; Sloboda et al, 1976)
Structural Microtubule Associated Proteins (MAPs) have been shown to: regulate actin cytoskeleton dynamics; be amenable to post-translational modifications which target them to membrane compartments; interact with a huge number of partners which are involved in neuroreceptor homeostasis and signaling cascades
If we focus on serotoninergic neurotransmission, serotonin biosynthesis and expression of the serotonin (5-HT) receptors are highly perturbed in MAP6 KO mice, with a 70% increase in 5HT-1A expression in the raphe nuclei for example (Fournet et al, 2010), as well as half reduction of serotonin (5-HT) in the substantia nigra, the ventral tegmental area and the hippocampus (Fournet et al, 2012b)
Summary
Microtubule-Associated Proteins (MAPs) were discovered in the context of the study of microtubule (MT) stability in neurons during the 1970s (Weingarten et al, 1975; Sloboda et al, 1976). Structural MAPs have been shown to: regulate actin cytoskeleton dynamics; be amenable to post-translational modifications which target them to membrane compartments; interact with a huge number of partners which are involved in neuroreceptor homeostasis and signaling cascades.
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