Microtubule-associated protein 1B (MAP1B)-deficient neurons show structural presynaptic deficiencies in vitro and altered presynaptic physiology

Abstract

Microtubule-associated protein 1B (MAP1B) is expressed predominantly during the early stages of development of the nervous system, where it regulates processes such as axonal guidance and elongation. Nevertheless, MAP1B expression in the brain persists in adult stages, where it participates in the regulation of the structure and physiology of dendritic spines in glutamatergic synapses. Moreover, MAP1B expression is also found in presynaptic synaptosomal preparations. In this work, we describe a presynaptic phenotype in mature neurons derived from MAP1B knockout (MAP1B KO) mice. Mature neurons express MAP1B, and its deficiency does not alter the expression levels of a subgroup of other synaptic proteins. MAP1B KO neurons display a decrease in the density of presynaptic and postsynaptic terminals, which involves a reduction in the density of synaptic contacts, and an increased proportion of orphan presynaptic terminals. Accordingly, MAP1B KO neurons present altered synaptic vesicle fusion events, as shown by FM4-64 release assay, and a decrease in the density of both synaptic vesicles and dense core vesicles at presynaptic terminals. Finally, an increased proportion of excitatory immature symmetrical synaptic contacts in MAP1B KO neurons was detected. Altogether these results suggest a novel role for MAP1B in presynaptic structure and physiology regulation in vitro.

The Role of the Microtubule Cytoskeleton in Neurodevelopmental Disorders

“…MAP1B is highly expressed during early neuronal development and is found to be enriched at growing axons, where it regulates axon outgrowth via its interaction with the MT cytoskeleton (Bouquet et al, 2004 ; Jayachandran et al, 2016 ). Neuronal subtypes derived from map1b −/− mice revealed several defects including higher collateral axon branching, improper growth cone turning, as well as abnormalities in synaptic vesicle fusion and synaptic plasticity, suggesting that MAP1B is necessary during these processes (Bouquet et al, 2004 ; Bodaleo et al, 2016 ). Furthermore, reduction of MAP1B was also shown to decrease MT growth speed in the proximal and distal axon shaft, suggesting that MAP1B may function as a regulator of MT dynamics during axon outgrowth (Tymanskyj et al, 2012 ).…”

Keratan sulfate (KS)‐proteoglycans and neuronal regulation in health and disease: the importance ofKS‐glycodynamics and interactive capability with neuroregulatory ligands

“…Free Ca promotes the disassembly of the ends of microtubule assemblies. The KSPG, microtubuleassociated protein 1B (MAP1B), and parvalbumin are microfibril associated, Ca 2+ binding proteins which stabilize the actin and tubulin cytoskeleton, Ca 2+ is a natural counterion to the KS chains of MAP1B which acts as a Ca 2+ reservoir (Li et al 2006;Cueille et al 2007;Barnat et al 2016;Bodaleo et al 2016;Takahara et al 2018). The assembly of actin and tubulin microtubules facilitates formation of lamellopodia and fillopodia essential for neuritogenesis and promoted by an up-regulation in MAP1B expression in neuritogenesis (Li et al 2006).…”

ReMAPping the microtubule landscape: How phosphorylation dictates the activities of microtubule‐associated proteins

“…MAPlA is expressed abundantly throughout development and into adulthood, when it is enriched specifically in dendrites (Fink et al, 1996). MAP1B is highly expressed during neuronal development, when it is localized to axons; then expression decreases after neuronal differentiation, but increases again in adulthood, when MAP1B has both dendritic and axonal functions (Kutschera et al, 1998;Gonzalez-Billault et al, 2001;Bodaleo et al, 2016). The shortest and least studied MAP1 member, MAP1S, is expressed in a variety of tissues including the brain, liver, spleen, heart, and other organs (Orban-Nemeth et al, 2005); recent studies indicate that it is involved in cell division, autophagy, and phagocytosis (Eriksson et al, 2007;Xie et al, 2011a;Xie et al, 2011b;Liu et al, 2012c;Tegha-Dunghu et al, 2014).…”