MAP9 single nucleotide polymorphism rs1058992 is a risk of EBV-associated gastric carcinoma in Chinese population

Liu, W; Xiao, Hong; Wu, Sheng Nan; Liu, H; Luo, Bin

doi:10.4149/av_2018_412

Cited by 5 publications

(2 citation statements)

References 29 publications

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“…Finally, MAP9 has been posited as a target for cancer treatment given its localization to the mitotic spindle (Liu et al, 2018;Wang et al, 2020;Zhang et al, 2022); however, we have shown that MAP9/MAPH-9 has an important role in cilia in supporting MTDs and modulating motors. Further work understanding MAP9/MAPH-9 will give insight into how MTDs are formed as well as be a protein of interest in understanding ciliopathies.…”

Section: Discussionmentioning

confidence: 86%

MAP9/MAPH-9 supports axonemal microtubule doublets and modulates motor movement

Tran

Ferguson

Cote

et al. 2023

Preprint

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Microtubule doublets (MTDs) are a well conserved compound microtubule structure found primarily in cilia. However, the mechanisms by which MTDs form and are maintained in vivo remain poorly understood. Here, we characterize microtubule-associated protein 9 (MAP9) as a novel MTD-associated protein. We demonstrate that C. elegans MAPH-9, a MAP9 homolog, is present during MTD assembly and localizes exclusively to MTDs, a preference that is in part mediated by tubulin polyglutamylation. Loss of MAPH-9 caused ultrastructural MTD defects, dysregulated axonemal motor velocity, and perturbed cilia function. As we found that the mammalian ortholog MAP9 localized to axonemes in cultured mammalian cells and mouse tissues, we propose that MAP9/MAPH-9 plays a conserved role in supporting the structure of axonemal MTDs and regulating ciliary motors.

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Section: Discussionmentioning

confidence: 86%

MAP9/MAPH-9 supports axonemal microtubule doublets and modulates motor movement

Tran

Ferguson

Cote

et al. 2023

Preprint

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“…This protein can directly interact with MTs via the C-terminal domain and depletion of MAP9 leads to delay of mitotic progression and failure of cytokinesis. Thus, associations between MAP9 dysfunction and the development of tumor cells has been reported in several types of carcinomas (Liu et al, 2018;Wang et al, 2020;Zhang et al, 2020). There are also several evidences that implicate MAP9 in the formation and function of primary cilia; specific expression of the C. elegans MAP9 ortholog MAPH-9 in ciliated sensory neurons (Jensen et al, 2016;Magescas et al, 2021); map9 depletion inducing developmental abnormalities related to cilia-dependent signaling pathways in zebrafish (Fontenille et al, 2014); and localization of MAP9 in the photoreceptor CC region of canine retina (Das et al, 2017).…”

Section: Introductionmentioning

confidence: 97%

Molecular characterization of MAP9 in the photoreceptor sensory cilia as a modifier in canine RPGRIP1-associated cone-rod dystrophy

Takahashi

Kwok

Sato

et al. 2023

Front. Cell. Neurosci.

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Photoreceptors possess a highly specialized primary cilium containing expanded ciliary membrane discs called the outer segment. The photoreceptor cilium is essential for the maintenance of the outer segment, and pathogenic variants in more than 50 cilia-related genes have been identified as causing non-syndromic inherited retinal diseases in patients. The retinitis pigmentosa GTPase regulator interacting protein 1 (RPGRIP1) is a structural protein localized to the photoreceptor cilium and biallelic RPGRIP1 variants have been associated with non-syndromic human inherited retinal diseases. In a canine cone-rod dystrophy model, a naturally occurring 44-bp exonic insertion in RPGRIP1 (RPGRIP1ins44/ins44) is the primary disease locus while an additional homozygous variant in MAP9 (microtubule associated protein 9) (MAP9aff/aff) acts as a modifier associated with early disease onset. MAP9 was originally identified as a microtubule-binding protein stabilizing microtubule structure during both mitosis and interphase in human cell lines. However, the roles of MAP9 in primary cilia, including photoreceptor neurosensory cilia, have not been well understood. Hence, we characterized the pathogenic phenotypes associated with homozygous MAP9 variant, and investigated the molecular function of MAP9 in primary cilia using the RPGRIP1-associated oligogenic canine cone-rod dystrophy model as well as cultured cells. Both functionally and structurally, the RPGRIP1ins44/ins44MAP9aff/aff retina exhibited progressive cone photoreceptor degeneration starting earlier than the retina affected by RPGRIP1ins44/ins44 alone. Based on immunostaining of canine retinal sections and cultured cells, we found that MAP9 is prominently localized in the basal body of primary cilia and played an important role in maintaining the structure of ciliary microtubule axoneme. These findings suggest that the affected MAP9, together with mutant RPGRIP1, is deprived of critical roles in cilia organization and maintenance resulting in altered cilia structure and function giving rise to early onset and accelerated disease progression in the RPGRIP1ins44/ins44MAP9aff/aff double homozygote cone-rod dystrophy canine model.

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