Dataset Information

Fascin- and ?-Actinin-Bundled Networks Contain Intrinsic Structural Features that Drive Protein Sorting.

ABSTRACT: Cells assemble and maintain functionally distinct actin cytoskeleton networks with various actin filament organizations and dynamics through the coordinated action of different sets of actin-binding proteins. The biochemical and functional properties of diverse actin-binding proteins, both alone and in combination, have been increasingly well studied. Conversely, how different sets of actin-binding proteins properly sort to distinct actin filament networks in the first place is not nearly as well understood. Actin-binding protein sorting is critical for the self-organization of diverse dynamic actin cytoskeleton networks within a common cytoplasm. Using in vitro reconstitution techniques including biomimetic assays and single-molecule multi-color total internal reflection fluorescence microscopy, we discovered that sorting of the prominent actin-bundling proteins fascin and ?-actinin to distinct networks is an intrinsic behavior, free of complicated cellular signaling cascades. When mixed, fascin and ?-actinin mutually exclude each other by promoting their own recruitment and inhibiting recruitment of the other, resulting in the formation of distinct fascin- or ?-actinin-bundled domains. Subdiffraction-resolution light microscopy and negative-staining electron microscopy revealed that fascin domains are densely packed, whereas ?-actinin domains consist of widely spaced parallel actin filaments. Importantly, other actin-binding proteins such as fimbrin and espin show high specificity between these two bundle types within the same reaction. Here we directly observe that fascin and ?-actinin intrinsically segregate to discrete bundled domains that are specifically recognized by other actin-binding proteins.

SUBMITTER: Winkelman JD

PROVIDER: S-EPMC5119644 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Publications

Fascin- and α-Actinin-Bundled Networks Contain Intrinsic Structural Features that Drive Protein Sorting.

Winkelman Jonathan D JD Suarez Cristian C Hocky Glen M GM Harker Alyssa J AJ Morganthaler Alisha N AN Christensen Jenna R JR Voth Gregory A GA Bartles James R JR Kovar David R DR

Current biology : CB 20160922 20

Cells assemble and maintain functionally distinct actin cytoskeleton networks with various actin filament organizations and dynamics through the coordinated action of different sets of actin-binding proteins. The biochemical and functional properties of diverse actin-binding proteins, both alone and in combination, have been increasingly well studied. Conversely, how different sets of actin-binding proteins properly sort to distinct actin filament networks in the first place is not nearly as wel ...[more]

PMID: 27666967

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Project description:Despite the effectiveness of surgical interventions for the treatment of intractable focal temporal lobe epilepsy (TLE), the substrates that support good outcomes are poorly understood. While algorithms have been developed for the prediction of either seizure or cognitive/psychiatric outcomes alone, no study has reported on the functional and structural architecture that supports joint outcomes. We measured key aspects of pre-surgical whole brain functional/structural network architecture and evaluated their ability to predict post-operative seizure control in combination with cognitive/psychiatric outcomes. Pre-surgically, we identified the intrinsic connectivity networks (ICNs) unique to each person through independent component analysis (ICA), and computed: (1) the spatial-temporal match between each person's ICA components and established, canonical ICNs, (2) the connectivity strength within each identified person-specific ICN, (3) the gray matter (GM) volume underlying the person-specific ICNs, and (4) the amount of variance not explained by the canonical ICNs for each person. Post-surgical seizure control and reliable change indices of change (for language [naming, phonemic fluency], verbal episodic memory, and depression) served as binary outcome responses in random forest (RF) models. The above functional and structural measures served as input predictors. Our empirically derived ICN-based measures customized to the individual showed that good joint seizure and cognitive/psychiatric outcomes depended upon higher levels of brain reserve (GM volume) in specific networks. In contrast, singular outcomes relied on systematic, idiosyncratic variance in the case of seizure control, and the weakened pre-surgical presence of functional ICNs that encompassed the ictal temporal lobe in the case of cognitive/psychiatric outcomes. Our data made clear that the ICNs differed in their propensity to provide reserve for adaptive outcomes, with some providing structural (brain), and others functional (cognitive) reserve. Our customized methodology demonstrated that when substantial unique, patient-specific ICNs are present prior to surgery there is a reliable association with poor post-surgical seizure control. These ICNs are idiosyncratic in that they did not match the canonical, normative ICNs and, therefore, could not be defined functionally, with their location likely varying by patient. This important finding suggested the level of highly individualized ICN's in the epileptic brain may signal the emergence of epileptogenic activity after surgery.

Dataset Information

Fascin- and ?-Actinin-Bundled Networks Contain Intrinsic Structural Features that Drive Protein Sorting.

Publications

Fascin- and α-Actinin-Bundled Networks Contain Intrinsic Structural Features that Drive Protein Sorting.

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