Dendrite tapering actuates a self-organizing signaling circuit for stochastic filopodia initiation in neurons

Autor(en): Mancinelli, Gloria
Lamparter, Lucas
Nosov, Georgii
Saha, Tanumoy
Pawluchin, Anna
Kurre, Rainer 
Rasch, Christiane
Ebrahimkutty, Mirsana
Klingauf, Juergen
Galic, Milos
Stichwörter: ACTIN DYNAMICS; ACTIVATION; BAR domain; CDC42; filopodia; INHIBITION; IRSP53; MECHANISMS; MEMBRANE; membrane curvature; MORPHOGENESIS; Multidisciplinary Sciences; neuron; Science & Technology - Other Topics; self-organization; SPINES; SYNAPTOGENESIS
Erscheinungsdatum: 2021
Herausgeber: NATL ACAD SCIENCES
Journal: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volumen: 118
Ausgabe: 43
Zusammenfassung: 
How signaling units spontaneously arise from a noisy cellular background is not well understood. Here, we show that stochastic membrane deformations can nucleate exploratory dendritic filopodia, dynamic actin-rich structures used by neurons to sample its surroundings for compatible transcellular contacts. A theoretical analysis demonstrates that corecruitment of positive and negative curvature-sensitive proteins to deformed membranes minimizes the free energy of the system, allowing the formation of longlived curved membrane sections from stochastic membrane fluctuations. Quantitative experiments show that once recruited, curvature-sensitive proteins form a signaling circuit composed of interlinked positive and negative actin-regulatory feedback loops. As the positive but not the negative feedback loop can sense the dendrite diameter, this self-organizing circuit determines filopodia initiation frequency along tapering dendrites. Together, our findings identify a receptor-independent signaling circuit that employs random membrane deformations to simultaneously elicit and limit formation of exploratory filopodia to distal dendritic sites of developing neurons.
ISSN: 00278424
DOI: 10.1073/pnas.2106921118j1of9

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