Investigations on Cellular Localization of Coiled-Coil Domain-Containing Protein 43 (CCDC43) Under Stress Conditions

Year 2025, Volume: 21 Issue: 3, 21 - 27, 26.09.2025

Merve Tuzlakoğlu Öztürk

https://doi.org/10.18466/cbayarfbe.1603514

Abstract

Coiled-coil domain containing (CCDC) family proteins regulate multiple biological functions in the cell. These domain structures have physical properties favorable for liquid-liquid phase separation (LLPS) phenomena, which play important roles in cell biology dynamics. LLPS is a fundamental mechanism in forming membrane-less organelles, including stress granules (SG) and P-body, nucleolus, PML nuclear body, Cajal bodies, nuclear speckles, and centrosomes. One of the new members of the CCDC protein family is CCDC43. In this study, sequence-based analyses of CCDC43, performed as a first step to understanding the role of CCDC43 in the cellular network, revealed the LLPS potential of the protein. We report that CCDC43, which has an evolutionarily conserved protein sequence, structurally possesses RNA-binding sites and its amino acid composition analysis may show an aggregation propensity and LLPS behavior under cellular conditions. CCDC43 is known to show a diffuse localization in the cytoplasm. We investigated whether this cellular localization is present in SGs whose formation is based on LLPS. We found that CCDC43 does not aggregate at SGs under given stress conditions. These data provide the first insights into the intracellular behavior and roles of CCDC43 in a disease-independent manner.

Keywords

CCDC43 , liquid-liquid phase separation , stress granules

Sarılı-sarmal domain içeren 43 proteininin (CCDC43) stres koşulları altında hücresel lokalizasyonu üzerine araştırmalar

Abstract

ÖZET
Sarılı-sarmal domain ailesi proteinleri hücrede çoklu biyolojik fonksiyonları düzenler. Bu domain yapıları, hücre biyolojisi dinamiklerinde önemli roller oynayan sıvı-sıvı faz ayrımı (LLPS) olayları için uygun fiziksel özelliklere sahiptir. LLPS, stres granülleri (SG) ve P-cisimciği, nükleolus, PML nükleer cisimciği, Cajal cisimcikleri, nükleer benekler ve sentrozomlar dahil olmak üzere zarsız organellerin oluşturulmasında temel bir mekanizmadır. CCDC protein ailesinin daha az çalışılmış üyelerinden biri CCDC43'tür. Bu çalışmada, CCDC43'ün hücresel ağdaki rolünü anlamak için ilk adım olarak gerçekleştirilen CCDC43'ün sekans bazlı analizleri, proteinin LLPS potansiyelini ortaya koymuştur. Evrimsel olarak korunmuş bir protein dizisine sahip olan CCDC43'ün yapısal olarak RNA bağlanma bölgelerine sahip olduğunu ve amino asit kompozisyon analizinin hücresel koşullar altında bir agregasyon eğilimi ve LLPS davranışı gösterebileceğini bildiriyoruz. CCDC43'ün sitoplazmada yaygın bir lokalizasyon gösterdiği bilinmektedir. Bu hücresel lokalizasyonun, oluşumu LLPS'ye dayanan SG'lerde mevcut olup olmadığını araştırdık. CCDC43'ün verilen stres koşulları altında SG'lerde toplanmadığını bulduk. Bu veriler, hastalıktan bağımsız bir şekilde CCDC43'ün hücre içi davranışı ve rolleri hakkında ilk bilgileri sağlamaktadır.

Keywords

CCDC43 , sıvı-sıvı faz ayrımı , stres granül

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