Mutations in PIH proteins MOT48, TWI1 and PF13 define common and unique steps for preassembly of each, different ciliary dynein

Autor: Yuya Yamasaki, Takahide Kon, Toshiki Yagi, Masahito Nagao, Winfield S. Sale, Shiho Yanagi, Yui Tanaka, Ryosuke Yamamoto
Rok vydání: 2020
Předmět:
Axoneme
Cytoplasm
Cancer Research
Physiology
Mutant
Chlamydomonas reinhardtii
QH426-470
Biochemistry
0302 clinical medicine
Cell Movement
Genetics (clinical)
Plant Proteins
Chlamydomonas Reinhardtii
0303 health sciences
Cilium
Microtubule Motors
Eukaryota
Plants
Cell biology
Phenotypes
Experimental Organism Systems
Cellular Structures and Organelles
Ciliary Motility Disorders
Research Article
Algae
Motor Proteins
Immunoblotting
Dynein
Molecular Probe Techniques
Motility
Biology
Research and Analysis Methods
Motor protein
03 medical and health sciences
Model Organisms
Molecular Motors
Plant and Algal Models
Genetics
Humans
Cilia
Molecular Biology Techniques
Molecular Biology
Swimming
Ecology
Evolution
Behavior and Systematics
030304 developmental biology
Biological Locomotion
Chlamydomonas
Organisms
Biology and Life Sciences
Proteins
Dyneins
Axonemal Dyneins
Cell Biology
biology.organism_classification
Cytoskeletal Proteins
Mutation
Animal Studies
030217 neurology & neurosurgery
Zdroj: PLoS Genetics, Vol 16, Iss 11, p e1009126 (2020)
PLoS Genetics
ISSN: 1553-7404
DOI: 10.1371/journal.pgen.1009126
Popis: Ciliary dyneins are preassembled in the cytoplasm before being transported into cilia, and a family of proteins containing the PIH1 domain, PIH proteins, are involved in the assembly process. However, the functional differences and relationships between members of this family of proteins remain largely unknown. Using Chlamydomonas reinhardtii as a model, we isolated and characterized two novel Chlamydomonas PIH preassembly mutants, mot48-2 and twi1-1. A new allele of mot48 (ida10), mot48-2, shows large defects in ciliary dynein assembly in the axoneme and altered motility. A second mutant, twi1-1, shows comparatively smaller defects in motility and dynein assembly. A double mutant mot48-2; twi1-1 displays greater reduction in motility and in dynein assembly compared to each single mutant. Similarly, a double mutant twi1-1; pf13 also shows a significantly greater defect in motility and dynein assembly than either parent mutant. Thus, MOT48 (IDA10), TWI1 and PF13 may define different steps, and have partially overlapping functions, in a pathway required for ciliary dynein preassembly. Together, our data suggest the three PIH proteins function in preassembly steps that are both common and unique for different ciliary dyneins.
Author summary Motile cilia are hair-like organelles that protrude from many eukaryotic cells, and play vital roles in organisms including cell motility, environmental sensing and removal of infectious materials. Motile cilia are driven by gigantic motor protein complexes, called ciliary dyneins, defects in which cause abnormal ciliary motility, ultimately resulting in human diseases collectively called primary ciliary dyskinesia (PCD). Ciliary dyneins are preassembled in the cytoplasm before being transported into cilia, and preassembly requires a family of potential co-chaperones, the PIH proteins. Mutations in the PIH proteins cause defective assembly of ciliary dyneins and can result in PCD. However, despite their importance, the precise functions, and functional relationships, between the PIH proteins are unclear. In this study, using Chlamydomonas reinhardtii, we assessed the functional relationship between three PIH proteins with respect to dynein preassembly and motility. We found that these PIH proteins have complicated and related roles in dynein assembly, possibly with each playing common and unique roles in dynein assembly. Our results provide new information on each conserved PIH protein for dynein assembly and provide a new understanding of PCD caused by PIH mutations.
Databáze: OpenAIRE
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