These authors contributed equally to this paper.
A Novel Hook-Related Protein Family and the Characterization of Hook-Related Protein 1
Article first published online: 22 APR 2005
Volume 6, Issue 6, pages 442–458, June 2005
How to Cite
Simpson, F., Martin, S., Evans, T. M., Kerr, M., James, D. E., Parton, R. G., Teasdale, R. D. and Wicking, C. (2005), A Novel Hook-Related Protein Family and the Characterization of Hook-Related Protein 1. Traffic, 6: 442–458. doi: 10.1111/j.1600-0854.2005.00289.x
- Issue published online: 22 APR 2005
- Article first published online: 22 APR 2005
- Received 16 December 2004, revised and accepted for publication 7 March 2005, published on-line 13 April 2005
- Hook protein;
- membrane trafficking;
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.