A Novel Hook-Related Protein Family and the Characterization of Hook-Related Protein 1

Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD 4072, Australia.
Traffic (Impact Factor: 4.35). 07/2005; 6(6):442-58. DOI: 10.1111/j.1600-0854.2005.00289.x
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The spatial organization of organelles within a cell is dependent on microtubules. Recently, members of the Hook family of proteins have been proposed to function in linking organelles to microtubules. We report the identification of a completely novel protein family, the Hook-related protein (HkRP) family, from which the Hook proteins have diverged. Bioinformatic analysis of the HkRP family revealed several conserved domains, including a unique C-terminal HkRP domain. The central region of each protein is comprised of an extensive coiled-coil domain, and the N-terminus contains a putative microtubule-binding domain. This domain has been shown to bind microtubules in the Hook protein and show that the HkRP1 protein is microtubule-associated. While endogenous HkRP1 has no distinct organelle association, expression of the C-terminal membrane-binding domain suggests a function of the HkRP1 in early endosome. Ultrastructural studies reveal that expression of the C-terminal HkRP1 domain causes an accumulation of internal membranes with an electron-dense coat. Co-localization studies show a concomitant redistribution of the early endosome marker sorting-nexin 1 but not the early endosome antigen-1 (EEA1). The steady-state distribution of the epidermal growth factor receptor is also specifically disrupted by expression of the C-terminal domain. We propose that HkRP1 is involved in the process of tubulation of sorting nexin-1 positive membranes from early endosome subdomains.

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Article: A Novel Hook-Related Protein Family and the Characterization of Hook-Related Protein 1

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    • "Since in both mecA 101 and mecA 20 mutations were introduced in a region that is common to all splice variants, both mecA alleles are expected to affect all Girdin isoforms. Both human and Drosophila Girdin have been reported to have N termini that are similar to the microtubule-binding domain of the Hook protein, an extensive central coiled-coil domain that is conserved in family-HkRP and more diverse C termini that specify the binding partners, such as actin (Simpson et al. 2005; Enomoto et al. 2006; Puseenam et al. 2009). "
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    • "Previous study indicated girdin as the component of dynamin complex (Simpson et al, 2005). To confirm this finding, the endogenous interaction between girdin and dynamin was investigated by co-immunoprecipitation (Co-IP). "
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    • "The name HkRP1 derives from the fact that the NT domain of Girdin shares high sequence homology with the microtubule-binding domain of the Hook protein family, which links microtubules to the membrane compartment. Although there is little evidence that Girdin directly binds microtubules, a report using inhibitors suggest a functional association between microtubules and Girdin [32]. Our results suggest that an interaction between Girdin and certain microtubule-binding proteins, identified as Girdin-interacting proteins, regulates microtubule dynamics and neuronal migration. "
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