Activity-Driven Dendritic Remodeling Requires Microtubule-Associated Protein 1A

Abstract

SummaryActivity-prompted dendritic remodeling [1, 2] leads to calcium-influx-dependent activation of signaling pathways within minutes and gene transcription within hours [3–6]. However, dendrite growth continues for days [2, 3, 7–9] and requires extension and stabilization of the cytoskeleton in nascent processes [8]. In addition to binding microtubules [10], microtubule-associated proteins (MAPs) associate with the actin cytoskeleton [11–13], anchor ion channels [14–19] and signaling complexes [17, 20], and modulate synaptic growth [21]. MAP2 is predominantly dendritic [22–24]. MAP1B is at postsynaptic densities (PSD) [25] and modulates ion channel activity [26], in addition to affecting axon growth [27, 28]. Less is known about MAP1A [10, 29–32], but it is also enriched in dendrites [29, 32] at input locations [33], including PSDs where MAP1A associates with channel complexes [19, 34] and the calcium sensor caldendrin [35]. MAP1A rescued hearing loss in tubby mice [36]. Here we show that MAP1A becomes enriched in dendrites concurrently with dendritic branching and synapse formation in the developing brain; that synaptic activity is required for establishing mature MAP1A expression levels; and that MAP1A expression is required for activity-dependent growth, branching, and stabilization of the dendritic arbor