Role of KASH domain lengths in the regulation of LINC complexes
| Autor: | Jahed, Zeinab, Hao, Hongyan, Thakkar, Vyom, Vu, Uyen T, Valdez, Venecia A, Rathish, Akshay, Tolentino, Chris, Kim, Samuel CJ, Fadavi, Darya, Starr, Daniel A, Mofrad, Mohammad RK |
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| Přispěvatelé: | Discher, Dennis |
| Rok vydání: | 2019 |
| Předmět: |
Nuclear Envelope
1.1 Normal biological development and functioning fungi Cell Membrane Amino Acid Motifs Biological Sciences Medical and Health Sciences Biomechanical Phenomena Structure-Activity Relationship Protein Domains Underpinning research Multiprotein Complexes Animals Humans Generic health relevance Amino Acid Sequence Caenorhabditis elegans Conserved Sequence Developmental Biology |
| Zdroj: | Molecular biology of the cell, vol 30, iss 16 |
| Popis: | The linker of the nucleoskeleton and cytoskeleton (LINC) complex is formed by the conserved interactions between Sad-1 and UNC-84 (SUN) and Klarsicht, ANC-1, SYNE homology (KASH) domain proteins, providing a physical coupling between the nucleoskeleton and cytoskeleton that mediates the transfer of physical forces across the nuclear envelope. The LINC complex can perform distinct cellular functions by pairing various KASH domain proteins with the same SUN domain protein. For example, in Caenorhabditis elegans, SUN protein UNC-84 binds to two KASH proteins UNC-83 and ANC-1 to mediate nuclear migration and anchorage, respectively. In addition to distinct cytoplasmic domains, the luminal KASH domain also varies among KASH domain proteins of distinct functions. In this study, we combined in vivo C. elegans genetics and in silico molecular dynamics simulations to understand the relation between the length and amino acid composition of the luminal KASH domain, and the function of the SUN-KASH complex. We show that longer KASH domains can withstand and transfer higher forces and interact with the membrane through a conserved membrane proximal EEDY domain that is unique to longer KASH domains. In agreement with our models, our in vivo results show that swapping the KASH domains of ANC-1 and UNC-83, or shortening the KASH domain of ANC-1, both result in a nuclear anchorage defect in C. elegans. |
| Databáze: | OpenAIRE |
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