ASB2α, an E3 Ubiquitin Ligase Specificity Subunit, Regulates Cell Spreading and Triggers Proteasomal Degradation of Filamins by Targeting the Filamin Calponin Homology 1 Domain

Razinia, Ziba; Baldassarre, Massimiliano; Cantelli, Gaia; Calderwood, David A.

doi:10.1074/jbc.m113.496604

Cited by 16 publications

(21 citation statements)

References 52 publications

(101 reference statements)

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“…Asb2 regulates actin cytoskeleton dynamics in hematopoietic cells and is implicated in the regulation of myogenic differentiation (35, 36). We observed a 2-fold suppression of ASB2 expression after 2 and 28 days of DOX-induced FST expression.…”

Section: Resultsmentioning

confidence: 99%

“…This suggests that ASB2’s target proteins are important mediators of muscle hypertrophy through a mechanism independent of the protein synthesis pathway. Currently, characterized targets of ASB2 include members of the filamin family (filaminA/B), which are critical in the organization and stability of f-actin fibers (35, 36, 43) and desmin (44). This supports our observation that protein synthesis activation through the mTOR pathway is insufficient to solely account for FST-stimulated muscle hypertrophy (32), and this model incorporates components beyond protein synthesis regulation, of which Asb2 is a critical member.…”

Section: Discussionmentioning

confidence: 99%

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Integrated expression analysis of muscle hypertrophy identifies Asb2 as a negative regulator of muscle mass

et al. 2016

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The transforming growth factor-β (TGF-β) signaling network is a critical regulator of skeletal muscle mass and function and, thus, is an attractive therapeutic target for combating muscle disease, but the underlying mechanisms of action remain undetermined. We report that follistatin-based interventions (which modulate TGF-β network activity) can promote muscle hypertrophy that ameliorates aging-associated muscle wasting. However, the muscles of old sarcopenic mice demonstrate reduced response to follistatin compared with healthy young-adult musculature. Quantitative proteomic and transcriptomic analyses of young-adult muscles identified a transcription/translation signature elicited by follistatin exposure, which included repression of ankyrin repeat and SOCS box protein 2 (Asb2). Increasing expression of ASB2 reduced muscle mass, thereby demonstrating that Asb2 is a TGF-β network–responsive negative regulator of muscle mass. In contrast to young-adult muscles, sarcopenic muscles do not exhibit reduced ASB2 abundance with follistatin exposure. Moreover, preventing repression of ASB2 in young-adult muscles diminished follistatin-induced muscle hypertrophy. These findings provide insight into the program of transcription and translation events governing follistatin-mediated adaptation of skeletal muscle attributes and identify Asb2 as a regulator of muscle mass implicated in the potential mechanistic dysfunction between follistatin-mediated muscle growth in young and old muscles.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Integrated expression analysis of muscle hypertrophy identifies Asb2 as a negative regulator of muscle mass

et al. 2016

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“…Rac1 promotes actin polymerization by participating in the modeling of two structures: lamellipodia and adhesion complexes linked with the plasma membrane . Therefore, we evaluated the increase of F‐actin in spermatozoa capacitated in the presence of Rac1 inhibitor (NSC23766).…”

Section: Resultsmentioning

confidence: 99%

“…The actin cytoskeleton remodeled in the apical region of the acrosome forms a new sperm domain, which could be stabilized by the actin cytoskeleton when associated with the plasma membrane. It is known that the crosslinking of actin filaments is stabilized and bound to the plasma membrane through filamin‐1, conferring rigidity and mechanical stability to the plasma membrane and the cellular cortex . Thus, to explore the relationship between the actin cytoskeleton and the membrane of the apical region of the acrosome, we studied the relationship between the actin cytoskeleton and filamin‐1 and the effects of inhibiting Rac1 in this relationship.…”

Section: Resultsmentioning

confidence: 99%

“…3.4 | Rac1 participates in the polymerization of actin in the apical region of the acrosome Rac1 promotes actin polymerization by participating in the modeling of two structures: lamellipodia and adhesion complexes linked with the plasma membrane. 26 Therefore, we evaluated the increase of F-actin in spermatozoa capacitated in the presence of Rac1 inhibitor (NSC23766). Staining with phalloidin-TRITC showed three different F-actin patterns (FAP): noncapacitated sperm showed a weak and homogeneous fluorescence throughout the cell (FAP1; Figure 4A).…”

Section: Rac1 Is Activated During Capacitationmentioning

confidence: 99%

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Rac1 is necessary for capacitation and acrosome reaction in guinea pig spermatozoa

Ramírez‐Ramírez

Salgado‐Lucio²,

Roa-Espitia³

et al. 2019

J of Cellular Biochemistry

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Actin cytoskeleton remodeling is a critical process for the acquisition of fertilizing capacity by spermatozoa during capacitation. However, the molecular mechanism that regulates this process has not been fully elucidated. In somatic cells, Ras‐related C3 botulinum toxin substrate 1 protein (Rac1) promotes the polymerization of actin by participating in the modeling of two structures: lamellipodia and adhesion complexes linked with the plasma membrane. Rac1 is expressed in mammalian spermatozoa; however, the role of Rac1 in sperm physiology is unknown. This study aimed to elucidate the participation of Rac1 in capacitation and acrosome reaction (AR). Rac1 was found to be dispersed throughout the acrosome and without changes in the middle piece. After 60 minutes of capacitation, Rac1 was found in the apical region of the acrosome only, which concurred with an increase in Rac1‐GTP. Rac1 inhibition prevented such changes. In the middle piece, Rac1 localization remained unchanged. Besides, Rac1 inhibition blocked capacitation and AR. The present study demonstrates that Rac1 participates only in the actin cytoskeleton remodeling that occurs in the acrosomal apical region during capacitation, a region where a large amount of actin is polymerized and shaped in a diadem‐like structure. Our data also show that this actin cytoskeleton organized by Rac1 interacts with filamin‐1, and such interaction was blocked by the inhibition of Rac1, which led to a different organization of the actin cytoskeleton. All these outcomes imply that the formation of an F‐actin cytoskeleton in the acrosomal apical region is a necessary event for capacitation and AR, and which is Rac1 driven.

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Transcriptomics of Meat Quality

Guo

Dalrymple

2017

New Aspects of Meat Quality

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ASB2α, an E3 Ubiquitin Ligase Specificity Subunit, Regulates Cell Spreading and Triggers Proteasomal Degradation of Filamins by Targeting the Filamin Calponin Homology 1 Domain

Cited by 16 publications

References 52 publications

Integrated expression analysis of muscle hypertrophy identifies Asb2 as a negative regulator of muscle mass

Integrated expression analysis of muscle hypertrophy identifies Asb2 as a negative regulator of muscle mass

Rac1 is necessary for capacitation and acrosome reaction in guinea pig spermatozoa

Transcriptomics of Meat Quality

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