Systematic Screens for Proteins That Interact with the Mucolipidosis Type IV Protein TRPML1

Spooner, Ellen; McLaughlin, Brooke M.; Lepow, Talya; Durns, Tyler A.; Randall, Justin; Upchurch, Cameron; Miller, Katherine; Campbell, Erin M.; Fares, Hanna
February 2013
PLoS ONE;Feb2013, Vol. 8 Issue 2, p1
Academic Journal
Mucolipidosis type IV is a lysosomal storage disorder resulting from mutations in the MCOLN1 gene, which encodes the endosomal/lysosomal Transient Receptor Potential channel protein mucolipin-1/TRPML1. Cells isolated from Mucolipidosis type IV patients and grown in vitro and in in vivo models of this disease both show several lysosome-associated defects. However, it is still unclear how TRPML1 regulates the transport steps implicated by these defects. Identifying proteins that associate with TRPML1 will facilitate the elucidation of its cellular and biochemical functions. We report here two saturation screens for proteins that interact with TRPML1: one that is based on immunoprecipitation/mass spectrometry and the other using a genetic yeast two-hybrid approach. From these screens, we identified largely non-overlapping proteins, which represent potential TRPML1-interactors., Using additional interaction assays on some of the potential interactors from each screen, we validated some proteins as candidate TRPML1 interactors In addition, our analysis indicates that each of the two screens not only identified some false-positive interactors, as expected from any screen, but also failed to uncover potential TRPML1 interactors. Future studies on the true interactors, first identified in these screens, will help elucidate the structure and function of protein complexes containing TRPML1.


Related Articles

  • Loss of TRPML1 promotes production of reactive oxygen species: is oxidative damage a factor in mucolipidosis type IV? COBLENTZ, Jessica; ST. CROIX, Claudette; KISELYOV, Kirill // Biochemical Journal;Jan2014, Vol. 457 Issue 2, p361 

    TRPML1 (transient receptor potentialmucolipin 1) is a lysosomal ion channel permeable to cations, including Fe2+. Mutations in MCOLN1, the gene coding for TRPML1, cause the LSD (lysosomal storage disease) MLIV (mucolipidosis type IV). The role of TRPML1 in the cell is disputed and the mechanisms...

  • A novel mutation in morquio syndrome. Yavari M.; Asadollahi S.; Hasheminasab S. H.; Harazi F. // Iranian Journal of Reproductive Medicine;Apr2015 Supplement, p91 

    Introduction: The Mucopolysaccharidoses (MPS) are a group of inherited metabolic disorders caused by a deficiency or malfunctioning of lysosomal enzymes which are needed to break down complex carbohydrates known as mucopolysaccharides or glycosaminoglycans (GAGs). Accumulation of GAGs causes a...

  • Proteomics of specific treatment-related alterations in Fabry disease: a strategy to identify biological abnormalities.  // Current Medical Literature: Lysosomal Storage Disease;2007, Vol. 7 Issue 2, p43 

    The article discusses the method of identifying treatment-related alterations in Anderson-Fabry diseases (AFD), an X-linked disorder caused by a deficiency of the lysosomal enzyme α-galactosidase A. It aims to identify proteins that differed in their relative abundance in the same patient...

  • Spectrum of lysosomal storage disorders at a medical genetics center in Northern India. Verma, Prashant; Ranganath, Prajnya; Dalal, Ashwin; Phadke, Shubha // Indian Pediatrics;Oct2012, Vol. 49 Issue 10, p799 

    Background: There is limited literature available on the phenotypic and mutation spectrum of Indian patients with Lysosomal storage disorders (LSD). Objective: To elucidate the clinical, biochemical and mutation spectrum and to study the management options in Indian patients with lysosomal...

  • Molecular analysis of mucopolysaccharidosis type I in Tunisia: identification of novel mutation and eight Novel polymorphisms. Chkioua, Latifa; Khedhiri, Souhir; Kassab, Asma; Bibi, Amina; Ferchichi, Salima; Froissart, Roseline; Vianey-Saban, Christine; Laradi, Sandrine; Miled, Abdelhedi // Diagnostic Pathology;2011 Supplement 1, Vol. 6 Issue Suppl 1, p39 

    Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder caused by a genetic defect in alpha-L-iduronidase (IDUA) which is involved in the degradation of dermatan and heparan sulfates. The disease has severe and milder phenotypic subtypes. The aim of this study...

  • Substrate Reduction Therapies for Mucopolysaccharidoses. Jakóbkiewicz-Banecka, Joanna; Piotrowska, Ewa; Gabig-Cimińska, Magdalena; Borysiewicz, Elżbieta; Słomińska-Wojewódzka, Monika; Narajczyk, Magdalena; Wƙgrzyn, Alicja; Wƙgrzyn, Grzegorz // Current Pharmaceutical Biotechnology;Nov2011, Vol. 12 Issue 11, p1860 

    Mucopolysaccharidoses (MPS) are inherited metabolic disorders, caused by mutations leading to dysfunction of one of enzymes involved in degradation of glycosaminoglycans (GAGs) in lysosomes. Due to their impaired degradation, GAGs accumulate in cells of patients, which results in dysfunction of...

  • LCR-initiated rearrangements at the IDS locus, completed with Alu-mediated recombination or non-homologous end joining. Oshima, Junko; Lee, Jennifer A; Breman, Amy M; Fernandes, Priscilla H; Babovic-Vuksanovic, Dusica; Ward, Patricia A; Wolfe, Lynne A; Eng, Christine M; del Gaudio, Daniela // Journal of Human Genetics;Jul2011, Vol. 56 Issue 7, p516 

    Mucopolysaccharidosis type II (MPS II) is caused by mutations in the IDS gene, which encodes the lysosomal enzyme iduronate-2-sulfatase. In ∼20% of MPS II patients the disorder is caused by gross IDS structural rearrangements. We identified two male cases harboring complex rearrangements...

  • Endo-Lysosomal Dysfunction in Human Proximal Tubular Epithelial Cells Deficient for Lysosomal Cystine Transporter Cystinosin. Ivanova, Ekaterina A.; De Leo, Maria Giovanna; Van Den Heuvel, Lambertus; Pastore, Anna; Dijkman, Henry; De Matteis, Maria Antonietta; Levtchenko, Elena N. // PLoS ONE;Mar2015, Vol. 10 Issue 3, p1 

    Nephropathic cystinosis is a lysosomal storage disorder caused by mutations in the CTNS gene encoding cystine transporter cystinosin that results in accumulation of amino acid cystine in the lysosomes throughout the body and especially affects kidneys. Early manifestations of the disease include...

  • In Vivo and Ex Vivo Evaluation of L-Type Calcium Channel Blockers on Acid β-Glucosidase in Gaucher Disease Mouse Models. Ying Sun; Liou, Benjamin; Quinn, Brian; Ran, Huimin; You-Hai Xu; Grabowski, Gregory A. // PLoS ONE;2009, Vol. 4 Issue 10, p1 

    Gaucher disease is a lysosomal storage disease caused by mutations in acid β-glucosidase (GCase) leading to defective hydrolysis and accumulation of its substrates. Two L-type calcium channel (LTCC) blockers—verapamil and diltiazem—have been reported to modulate endoplasmic...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics