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A Novel Hook‐Related Protein Family and the Characterization of Hook‐Related Protein 1
Author(s) -
Simpson Fiona,
Martin Sally,
Evans Timothy M.,
Kerr Markus,
James David E.,
Parton Robert G.,
Teasdale Rohan D.,
Wicking Carol
Publication year - 2005
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2005.00289.x
Subject(s) - endosome , microtubule , biology , microbiology and biotechnology , egf like domain , organelle , sorting nexin , protein family , protein domain , biochemistry , gene , intracellular
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.