AHNAK1 and AHNAK2 are costameric proteins: AHNAK1 affects transverse skeletal muscle fiber stiffness

Marg, Andreas; Haase, Hannelore; Neumann, Tanja; Kouno, Michiyoshi; Morano, Ingo

doi:10.1016/j.bbrc.2010.09.030

Cited by 27 publications

(34 citation statements)

References 21 publications

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“…To examine the expression and localization of Ahnak1 and Ahnak2 in murine femoral arteries, we employed previously characterized antibodies developed against the specific carboxy-terminal ends of Ahnak1 and Ahnak2 [5,32]. Confocal microscopy of immunostained sections of murine femoral artery showed prominent expression of Ahnak1 in vascular endothelium (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The antibodies against Ahnak1 and Ahnak2 were raised in rabbits using synthetic peptides corresponding to specific sequences in the carboxy-terminal portion of murine large Ahnak1 (L-Ahnak NP_033773.1; KKSRLSSSSSNDSG) and Ahnak2 (AHNAK2 XP_006516522.1; AHNAK2 isoform X1 XP_006543088.1 and X2 XP_006543089.1; GSEAMVASSARTEL), respectively. The antibodies were affinity-purified on the respective peptides, and have been described elsewhere [5,32]. TUNEL assay (in situ cell death detection kit, Roche) was done according to the manufacturer's protocol.…”

Section: Methodsmentioning

confidence: 99%

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Protective Function of Ahnak1 in Vascular Healing after Wire Injury

Haase

Rüder²,

Haase³

et al. 2017

J Vasc Res

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Aim: Vascular remodeling following injury substantially accounts for restenosis and adverse clinical outcomes. In this study, we investigated the role of the giant scaffold protein Ahnak1 in vascular healing after endothelial denudation of the murine femoral artery. Methods: The spatiotemporal expression pattern of Ahnak1 and Ahnak2 was examined using specific antibodies and real-time quantitative PCR. Following wire-mediated endothelial injury of Ahnak1-deficient mice and wild-type (WT) littermates, the processes of vascular healing were analyzed. Results: Ahnak1 and Ahnak2 showed a mutually exclusive vascular expression pattern, with Ahnak1 being expressed in the endothelium and Ahnak2 in the medial cells in naïve WT arteries. After injury, a marked increase of Ahnak1- and Ahnak2-positive cells at the lesion site became evident. Both proteins showed a strong upregulation in neointimal cells 14 days after injury. Ahnak1-deficient mice showed delayed vascular healing and dramatically impaired re-endothelialization that resulted in prolonged adverse vascular remodeling, when compared to the WT littermates. Conclusion: The large scaffold and adaptor proteins Ahnak1 and Ahnak2 exhibit differential expression patterns and functions in naïve and injured arteries. Ahnak1 plays a nonredundant protective role in vascular healing.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Protective Function of Ahnak1 in Vascular Healing after Wire Injury

Haase

Rüder²,

Haase³

et al. 2017

J Vasc Res

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“…AHNAK2 is a 600 kDa protein that is expressed in the majority of muscle cells and has a similar function to AHNAK1: It regulates the contraction coupling of myocardial cells through its PSD-95/Discs-large/ZO-1 structural domain (49,50). In addition, AHNAK2 is a constituent of costameres in skeletal muscle and may link the extracellular matrix with the cytoskeleton (19,51). Previous studies have identified that PPL and AHNAK1 affect the formation of the ezrin, PPL, periaxin and desmoyokin skeletal protein complex (52).…”

Section: Discussionmentioning

confidence: 99%

iTRAQ-coupled 2D LC/MS-MS analysis of CXCR7-transfected papillary thyroid carcinoma cells: A new insight into CXCR7 regulation of papillary thyroid carcinoma progression and identification of potential biomarkers

et al. 2017

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Abstract. Previous studies have demonstrated that C-X-C chemokine receptor type 7 (CXCR7) regulates papillary thyroid carcinoma (PTC) growth and metastasis; however, the molecular mechanisms underlying this regulation remain unclear. In the present study, the protein expression profiles of the PTC cell line GLAG-66 and GLAG-66 cells stably transfected with CXCR7 cDNA were analyzed and compared using isobaric tag for relative and absolute quantification-coupled two-dimensional liquid chromatography-tandem mass spectrometry. In total, 2,983 proteins were quantified and 130 proteins were identified to be differentially expressed, of which 87 were significantly upregulated and 43 were significantly downregulated. Gene Ontology enrichment analysis revealed that the differentially expressed proteins were primarily enriched in a number of biological processes, including metabolism-related processes, cellular component organization, transport, cellular development process and the immune response. The differentially expressed proteins identified included fibronectin 1, basigin, periplakin and serpin family B member 5, all of which are associated with cellular junctions and cancer progression. In addition, transgelin-2 and AHNAK nucleoprotein 2 were identified as potential novel biomarkers for the prognosis and treatment of PTC. IntroductionThyroid carcinoma is the most common endocrine neoplasm, of which papillary thyroid carcinoma (PTC) is the most common pathological type, accounting for 80% of thyroid carcinomas (1,2). Cervical lymph node metastasis is a typical clinical feature of PTC and is a risk factor for increased recurrence rates and decreased survival rates (3,4). Therefore, the identification of potential biomarkers that may be used to assess the prognosis and treatment of PTC is required.Chemokines and their receptors serve critical roles in the development and progression of tumors (5), particularly in promoting cell migration (6). Previous studies have demonstrated that C-X-C chemokine receptor type 7 (CXCR7) expression serves a role in tumor cell proliferation, angiogenesis, invasion and metastasis (7-10). A previous study from our laboratory demonstrated that CXCR7 was overexpressed in PTC tissue compared with peritumoral non-malignant tissue and benign thyroid lesion tissue, and the expression of CXCR7 was positively associated with cervical lymph node metastasis (11). Furthermore, knockdown of CXCR7 in PTC cells has been demonstrated to suppress cell proliferation and invasion, and promote apoptosis (12), which suggests that CXCR7 is involved in the regulation of PTC progression.In a previous study, to reveal the molecular mechanisms underlying CXCR7-mediated regulation of PTC progression, a gene microarray analysis was performed to detect changes in gene expression between PTC cells and PTC cells transfected with CXCR7. The results demonstrated that CXCR7 promotes the growth and metastasis of PTC via the activation of the phosphoinositide 3-kinase (PI3K)/RAC-α serine/threonine-protein kinase (AKT)/nuc...

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“…According to Huang et al (57), AHNAK and dysferlin colocalize at the sarcolemmal membrane, where dysferlin was shown to interact with α-tubulin (58). A recent publication clearly demonstrated that AHNAK is also found in the costameric network and is not present in the T-tubule system, leading to the hypothesis that AHNAK is involved in fiber stiffness (59). Finally, dysferlin has binding partners that play direct and indirect roles in membrane repair, such as MG53 (also called TRIM72).…”

Section: Introductionmentioning

confidence: 99%

Translational Research and Therapeutic Perspectives in Dysferlinopathies

Barthélémy

Wein

Krahn

et al. 2011

Mol Med

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Dysferlinopathies are autosomal recessive disorders caused by mutations in the dysferlin (DYSF) gene, encoding the dysferlin protein. DYSF mutations lead to a wide range of muscular phenotypes, with the most prominent being Miyoshi myopathy (MM) and limb girdle muscular dystrophy type 2B (LGMD2B) and the second most common being LGMD. Symptoms generally appear at the end of childhood and, although disease progression is typically slow, walking impairments eventually result. Dysferlin is a modular type II transmembrane protein for which numerous binding partners have been identified. Although dysferlin function is only partially elucidated, this large protein contains seven calcium sensor C2 domains, shown to play a key role in muscle membrane repair. On the basis of this major function, along with detailed clinical observations, it has been possible to design various therapeutic approaches for dysferlin-deficient patients. Among them, exon-skipping and minigene transfer strategies have been evaluated at the preclinical level and, to date, represent promising approaches for clinical trials. This review aims to summarize the pathophysiology of dysferlinopathies and to evaluate the therapeutic potential for treatments currently under development.

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AHNAK1 and AHNAK2 are costameric proteins: AHNAK1 affects transverse skeletal muscle fiber stiffness

Cited by 27 publications

References 21 publications

Protective Function of Ahnak1 in Vascular Healing after Wire Injury

Protective Function of Ahnak1 in Vascular Healing after Wire Injury

iTRAQ-coupled 2D LC/MS-MS analysis of CXCR7-transfected papillary thyroid carcinoma cells: A new insight into CXCR7 regulation of papillary thyroid carcinoma progression and identification of potential biomarkers

Translational Research and Therapeutic Perspectives in Dysferlinopathies

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