TPM3 and TPM4 gene products segregate to the postsynaptic region of central nervous system synapses

Guven, Kim; Gunning, Peter W.; Fath, Thomas

doi:10.4161/bioa.1.6.19336

Cited by 26 publications

(28 citation statements)

References 39 publications

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“…These preferentially stabilized filaments could accumulate thereby altering their relative distribution. Tpms have isoform-specific expression and localization in neurons [Had et al, 1994;Schevzov et al, 1997;Guven et al, 2011]. TPM1 gene products (Tpm1.10, Tpm1.11, and Tpm1.12, previously TMBr1, TMBr2, and TMBr3, respectively) were found to localize to presynaptic compartments while TPM3 (Tpm3.1-9, previously TM5NM1-9) and TPM4 (Tpm4.2, previously TM4) gene products localize to dendritic spines.…”

Section: Discussionmentioning

confidence: 99%

Tropomodulin isoforms utilize specific binding functions to modulate dendrite development

et al. 2016

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Tropomodulins (Tmods) cap F-actin pointed ends and have altered expression in the brain in neurological diseases. The function of Tmods in neurons has been poorly studied and their role in neurological diseases is entirely unknown. In this paper we show that Tmod1 and Tmod2, but not Tmod3, are positive regulators of dendritic complexity and dendritic spine morphology. Tmod1 increases dendritic branching distal from the cell body and the number of filopodia/thin spines. Tmod2 increases dendritic branching proximal to the cell body and the number of mature dendritic spines. Tmods utilize two actin-binding sites and two tropomyosin (Tpm)-binding sites to cap F-actin. Overexpression of Tmods with disrupted Tpm-binding sites indicates that Tmod1 and Tmod2 differentially utilize their Tpm- and actin-binding sites to affect morphology. Disruption of Tmod1’s Tpm-binding sites abolished the overexpression phenotype. In contrast, overexpression of the mutated Tmod2 caused the same phenotype as wild type overexpression. Proximity ligation assays indicate that the mutated Tmods are shuttled similarly to wild type Tmods. Our data begins to uncover the roles of Tmods in neural development and the mechanism by which Tmods alter neural morphology. These observations in combination with altered Tmod expression found in several neurological diseases also suggest that dysregulation of Tmod expression may be involved in the pathology of these diseases.

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Section: Discussionmentioning

confidence: 99%

Tropomodulin isoforms utilize specific binding functions to modulate dendrite development

et al. 2016

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“…This is a clear indicator that Tmod-Tpm interactions are important in spinogenesis and depend on Tmod isoform. Previous work has shown the presence of products from both the TPM3 and the TPM4 gene in the postsynaptic compartment (Guven et al, 2011; Had et al, 1994). The presence of a diverse set of Tpm isoforms in this compartment and their differential interaction with Tmod1 and Tmod2 provides a potential mechanism of fine-tuning the regulation of the synaptic actin filament system.…”

Section: Tropomodulins and Tropomyosins Regulate Neuronal Morphologymentioning

confidence: 98%

Actin regulation by tropomodulin and tropomyosin in neuronal morphogenesis and function

Gray

Kostyukova

Fath

2017

Molecular and Cellular Neuroscience

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Actin is a profoundly influential protein; it impacts, among other processes, membrane morphology, cellular motility, and vesicle transport. Actin can polymerize into long filaments that push on membranes and provide support for intracellular transport. Actin filaments have polar ends: the fast-growing (barbed) end and the slow-growing (pointed) end. Depolymerization from the pointed end supplies monomers for further polymerization at the barbed end. Tropomodulins (Tmods) cap pointed ends by binding onto actin and tropomyosins (Tpms). Tmods and Tpms have been shown to regulate many cellular processes; however, very few studies have investigated their joint role in the nervous system. Recent data directly indicate that they can modulate neuronal morphology. Additional studies suggest that Tmod and Tpm impact molecular processes influential in synaptic signaling. To facilitate future research regarding their joint role in actin regulation in the nervous system, we will comprehensively discuss Tpm and Tmod and their known functions within molecular systems that influence neuronal development.

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“…Tmods can cap the pointed ends with and without the presence of tropomyosins (Tms), but binding of Tmods to tropomyosins greatly enhances its minus end capping activity. Several brain-specific Tms have been identified, of which Tms from TPM3 and TPM4 genes have shown to localize to postsynaptic spines (Guven et al, 2011). Whether these Tms are present and function in nerve growth cones during development remains unknown.…”

Section: Growth Cone Motility: Monomers and Capsmentioning

confidence: 99%

Actin-based growth cone motility and guidance

Omotade

Pollitt

Zheng

2017

Molecular and Cellular Neuroscience

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Nerve growth cones, the dilated tip of developing axons, are equipped with exquisite abilities to sense environmental cues and to move rapidly through complex terrains of developing brain, leading the axons to their specific targets for precise neuronal wiring. The actin cytoskeleton is the major component of the growth cone that powers its directional motility. Past research has provided significant insights into the mechanisms by which growth cones translate extracellular signals into directional migration. In this review, we summarize the actin-based mechanisms underlying directional growth cone motility, examine novel findings, and discuss the outstanding questions concerning the actin-based growth cone behaviors.

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TPM3 and TPM4 gene products segregate to the postsynaptic region of central nervous system synapses

Cited by 26 publications

References 39 publications

Tropomodulin isoforms utilize specific binding functions to modulate dendrite development

Tropomodulin isoforms utilize specific binding functions to modulate dendrite development

Actin regulation by tropomodulin and tropomyosin in neuronal morphogenesis and function

Actin-based growth cone motility and guidance

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