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Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1.

ABSTRACT: Mutations of the inositol 5' phosphatase oculocerebrorenal syndrome of Lowe (OCRL) give rise to the congenital X-linked disorders oculocerebrorenal syndrome of Lowe and Dent disease, two conditions giving rise to abnormal kidney proximal tubule reabsorption, and additional nervous system and ocular defects in the case of Lowe syndrome. Here, we identify two closely related endocytic proteins, Ses1 and Ses2, which interact with the ASH-RhoGAP-like (ASPM-SPD-2-Hydin homology and Rho-GTPase Activating Domain-like) domain of OCRL. The interaction is mediated by a short amino acid motif similar to that used by the rab-5 effector APPL1 (Adaptor Protein containing pleckstrin homology [PH] domain, PTB domain and Leucine zipper motif 1) APPL1 for OCRL binding. Ses binding is mutually exclusive with APPL1 binding, and is disrupted by the same missense mutations in the ASH-RhoGAP-like domain that also disrupt APPL1 binding. Like APPL1, Ses1 and -2 are localized on endosomes but reside on different endosomal subpopulations. These findings define a consensus motif (which we have called a phenylalanine and histidine [F&H] motif) for OCRL binding and are consistent with a scenario in which Lowe syndrome and Dent disease result from perturbations at multiple sites within the endocytic pathway.

SUBMITTER: Swan LE

PROVIDER: S-EPMC2840420 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1.

Swan Laura E LE Tomasini Livia L Pirruccello Michelle M Lunardi Joël J De Camilli Pietro P

Proceedings of the National Academy of Sciences of the United States of America 20100202 8

Mutations of the inositol 5' phosphatase oculocerebrorenal syndrome of Lowe (OCRL) give rise to the congenital X-linked disorders oculocerebrorenal syndrome of Lowe and Dent disease, two conditions giving rise to abnormal kidney proximal tubule reabsorption, and additional nervous system and ocular defects in the case of Lowe syndrome. Here, we identify two closely related endocytic proteins, Ses1 and Ses2, which interact with the ASH-RhoGAP-like (ASPM-SPD-2-Hydin homology and Rho-GTPase Activat ...[more]

PMID: 20133602

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Project description:Odorant-binding proteins (OBPs) are of great importance for survival and reproduction since they participate in initial steps of the olfactory signal transduction cascade, solubilizing and transporting chemical signals to the olfactory receptors. A comparative analysis of OBPs between closely related species may help explain how these genes evolve and are maintained under natural selection and how differences in these proteins can affect olfactory responses. We studied OBP genes in the closely related species Anastrepha fraterculus and A. obliqua, which have different host preferences, using data from RNA-seq cDNA libraries of head and reproductive tissues from male and female adults, aiming to understand the speciation process occurred between them.We identified 23 different OBP sequences from Anastrepha fraterculus and 24 from A. obliqua, which correspond to 20 Drosophila melanogaster OBP genes. Phylogenetic analysis separated Anastrepha OBPs sequences in four branches that represent four subfamilies: classic, minus-C, plus-C and dimer. Both species showed five plus-C members, which is the biggest number found in tephritids until now. We found evidence of positive selection in four genes and at least one duplication event that preceded the speciation of these two species. Inferences on tertiary structures of putative proteins from these genes revealed that at least one positively selected change involves the binding cavity (the odorant binding region) in the plus-C OBP50a.A. fraterculus and A. obliqua have a bigger OBP repertoire than the other tephritids studied, though the total number of Anastrepha OBPs may be larger, since we studied only a limited number of tissues. The contrast of these closely related species reveals that there are several amino acid changes between the homologous genes, which might be related to their host preferences. The plus-C OBP that has one amino acid under positive selection located in the binding cavity may be under a selection pressure to recognize and bind a new odorant. The other positively selected sites found may be involved in important structural and functional changes, especially ones in which site-specific changes would radically change amino acid properties.

Dataset Information

Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1.

Publications

Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1.

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