A minimal actomyosin-based model predicts the dynamics of filopodia on neuronal dendrites

Autor: Tatyana Svitkina, Ji Yu, Nadia Efimova, Olena Marchenko, Charles W. Wolgemuth, Vladimir Rodionov, Sulagna Das, Leslie M. Loew, Igor L. Novak
Rok vydání: 2017
Předmět:
Zdroj: Molecular Biology of the Cell
ISSN: 1939-4586
1059-1524
DOI: 10.1091/mbc.e16-06-0461
Popis: A combination of computational and experimental approaches is used to show that the complex dynamics of dendritic filopodia, which is essential for synaptogenesis, is explained by a conceptually simple interplay among actin retrograde flow, myosin contractility, and substrate adhesion.
Dendritic filopodia are actin-filled dynamic subcellular structures that sprout on neuronal dendrites during neurogenesis. The exploratory motion of the filopodia is crucial for synaptogenesis, but the underlying mechanisms are poorly understood. To study filopodial motility, we collected and analyzed image data on filopodia in cultured rat hippocampal neurons. We hypothesized that mechanical feedback among the actin retrograde flow, myosin activity, and substrate adhesion gives rise to various filopodial behaviors. We formulated a minimal one-dimensional partial differential equation model that reproduced the range of observed motility. To validate our model, we systematically manipulated experimental correlates of parameters in the model: substrate adhesion strength, actin polymerization rate, myosin contractility, and the integrity of the putative microtubule-based barrier at the filopodium base. The model predicts the response of the system to each of these experimental perturbations, supporting the hypothesis that our actomyosin-driven mechanism controls dendritic filopodia dynamics.
Databáze: OpenAIRE