Projects per year
Abstract
α-actinin (ACTN) is a pivotal member of the actin-binding protein family, crucial for the anchoring and organization of actin filaments within the cytoskeleton. Four isoforms of α-actinin exist: two non-muscle isoforms (ACTN1 and ACTN4) primarily associated with actin stress fibers and focal adhesions, and two muscle-specific isoforms (ACTN2 and ACTN3) localized to the Z-disk of the striated muscle. Although these isoforms share structural similarities, they exhibit distinct functional characteristics that reflect their specialized roles in various tissues. Genetic variants in α-actinin isoforms have been implicated in a range of pathologies, including cardiomyopathies, thrombocytopenia, and non-cardiovascular diseases, such as nephropathy. However, the precise impact of these genetic variants on the α-actinin structure and their contribution to disease pathogenesis remains poorly understood. This review provides a comprehensive overview of the structural and functional attributes of the four α-actinin isoforms, emphasizing their roles in actin crosslinking and sarcomere stabilization. Furthermore, we present detailed structural modeling of select ACTN1 and ACTN2 variants to elucidate mechanisms underlying disease pathogenesis, with a particular focus on macrothrombocytopenia and hypertrophic cardiomyopathy. By advancing our understanding of α-actinin’s role in both normal cellular function and disease states, this review lays the groundwork for future research and the development of targeted therapeutic interventions.
Original language | English |
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Article number | e202413684 |
Journal | Journal of General Physiology |
Volume | 157 |
Issue number | 2 |
DOIs | |
Publication status | Published - 7 Feb 2025 |
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Understanding the mechano-signalling role of the Z-disc in the pathogenesis of Hypertrophic Cardiomyopathy
Gehmlich, K. (Principal Investigator)
1/09/24 → 28/12/28
Project: Research
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The interactions between filamin C and small heat shock proteins in cardiac mechanosignalling
Gehmlich, K. (Principal Investigator)
1/06/21 → 30/11/24
Project: Research Councils
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Investigating the role of SLFN14 in megakaryocyte and platelet biology
Morgan, N. (Principal Investigator) & Watson, S. (Co-Investigator)
4/06/18 → 3/06/21
Project: Research
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Functional investigation of SLFN14 in megakaryocyte and platelet biology
Morgan, N. (Principal Investigator) & Gough, R. (Co-Investigator)
22/08/17 → 20/02/20
Project: Research