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Identification of a novel light intermediate chain (D2LIC) for mammalian cytoplasmic dynein 2.

ABSTRACT: The diversity of dynein's functions in mammalian cells is a manifestation of both the existence of multiple dynein heavy chain isoforms and an extensive set of associated protein subunits. In this study, we have identified and characterized a novel subunit of the mammalian cytoplasmic dynein 2 complex. The sequence similarity between this 33-kDa subunit and the light intermediate chains (LICs) of cytoplasmic dynein 1 suggests that this protein is a dynein 2 LIC (D2LIC). D2LIC contains a P-loop motif near its NH(2) terminus, and it shares a short region of similarity to the yeast GTPases Spg1p and Tem1p. The D2LIC subunit interacts specifically with DHC2 (or cDhc1b) in both reciprocal immunoprecipitations and sedimentation assays. The expression of D2LIC also mirrors that of DHC2 in a variety of tissues. D2LIC colocalizes with DHC2 at the Golgi apparatus throughout the cell cycle. On brefeldin A-induced Golgi fragmentation, a fraction of D2LIC redistributes to the cytoplasm, leaving behind a subset of D2LIC that is localized around the centrosome. Our results suggest that D2LIC is a bona fide subunit of cytoplasmic dynein 2 that may play a role in maintaining Golgi organization by binding cytoplasmic dynein 2 to its Golgi-associated cargo.

SUBMITTER: Grissom PM

PROVIDER: S-EPMC99601 | biostudies-literature | 2002 Mar

REPOSITORIES: biostudies-literature

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Identification of a novel light intermediate chain (D2LIC) for mammalian cytoplasmic dynein 2.

Grissom Paula M PM Vaisberg Eugeni A EA McIntosh J Richard JR

Molecular biology of the cell 20020301 3

The diversity of dynein's functions in mammalian cells is a manifestation of both the existence of multiple dynein heavy chain isoforms and an extensive set of associated protein subunits. In this study, we have identified and characterized a novel subunit of the mammalian cytoplasmic dynein 2 complex. The sequence similarity between this 33-kDa subunit and the light intermediate chains (LICs) of cytoplasmic dynein 1 suggests that this protein is a dynein 2 LIC (D2LIC). D2LIC contains a P-loop m ...[more]

PMID: 11907264

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Project description:Dynein transport along the cytoskeletal microtubules towards the minus end is essential for cell division, cell migration and other basic cellular functions. Dynein cytoplasmic 1 light intermediate chain 1 (DYNC1LI1) has been previously associated with pancreatic ductal adenocarcinoma, hepatocellular carcinoma and prostate cancer. Cytoskeletal structures are involved in the regulation of the mucosal barrier integrity. Thus, improving our understanding of the molecular mechanisms that regulate the mucosal barrier is critical for cancer management and treatment. The present study aimed to investigate DYNC1LI1 expression in colorectal cancer (CRC) tissues. The American Joint Committee on Cancer Stage II CRC cell line LS 174T was used to determine the association between the cellular expression levels of DYNC1LI1 and different types of mucin (MUC) by reverse transcription‑quantitative PCR. The role of DYNC1LI1 in cell chemosensitivity and proliferation was also evaluated in the presence of the DNA analog 5‑fluorouracil (5‑FU) or the platinum‑based drug, oxaliplatin by the MTT assay. LS 174T cells with decreased expression levels of DYNC1LI1 were discovered to be more sensitive to 5‑FU compared with LS 174T cells with endogenous DYNC1LI1 expression levels. Moreover, LS 174T cells transfected with short hairpin RNA targeting DYNC1LI1 were associated with low MUC1 and high MUC2, MUC4 and MUC5AC expression levels. Notably, the CRC cells with low MUC1 expression levels and high expression levels of the other MUCs (MUC2, MU4 and MUC5AC) were shown to benefit from 5‑FU treatment. In conclusion, the findings of the present study have suggested that DYNC1LI1 expression may be significantly associated with MUC expression levels and may be used to predict the chemotherapeutic efficiency. However, additional functional studies and clinical reports are required for an improved understanding of the significance of these molecular interactions in tumorigenesis.

Dataset Information

Identification of a novel light intermediate chain (D2LIC) for mammalian cytoplasmic dynein 2.

Publications

Identification of a novel light intermediate chain (D2LIC) for mammalian cytoplasmic dynein 2.

Similar Datasets

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