Membrane Traffic and Disease

Nuno Cláudio, Universidade Nova de Lisboa, Lisboa, Portugal
Francisco JC Pereira, Universidade Nova de Lisboa, Lisboa, Portugal
Duarte C Barral, Universidade Nova de Lisboa, Lisboa, Portugal

Published online: November 2014

DOI: 10.1002/9780470015902.a0020892

Abstract

Membrane traffic is a highly regulated process that ensures the communication between membrane‐bound compartments while maintaining their specific protein and lipid composition. It can be divided into four steps: cargo sorting and budding of a vesicle from a donor compartment, transport along the cytoskeleton, tethering and docking to an acceptor compartment, and finally fusion with the acceptor compartment. Importantly, defects in any of these steps can lead to diseases that affect different tissues and organs. At the subcellular level, several of these diseases affect compartments from specialized cell types known as lysosome‐related organelles. Moreover, the dysfunction of membrane traffic processes required ubiquitously can lead to restricted phenotypes, underscoring the redundancy of these processes and/or the sensitivity of certain cell types to their impairment. Thus, the study of the diseases caused by defects in membrane traffic provides an opportunity to understand its role in normal cell physiology and discover novel therapies.

Key Concepts:

  • Defects in any of the steps of vesicular traffic can lead to disease.

  • Vesicular traffic regulation shows redundancy.

  • Defects in ubiquitously‐expressed proteins can result in a tissue‐restricted phenotype.

  • Lysosome‐related organelles are commonly affected upon impairment of vesicular traffic.

  • Several diseases are caused by defects in different proteins involved in the same biological process/pathway.

Keywords: vesicular traffic; Rab; Arf; SNARE ; coat protein; kinesin; myosin; dynein; small G protein; lysosome‐related organelle

Figure 1.

Membrane traffic steps and diseases caused by their impairment. Nascent‐coated vesicles bud from donor compartments and are transported along the cytoskeleton via molecular motor proteins. Vesicles are tethered and docked to the acceptor compartments before SNARE‐mediated fusion with the latter. Diseases that are caused by dysfunction of these steps are indicated. CEDNIK – Cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma syndrome; CLSD – Cranio‐lenticulo‐sutural dysplasia; CMRD – Chylomicron retention disease; CMT – Charcot‐Marie‐Tooth type 2; FHL – Familial hemophagocytic lymphohistiocytosis; GS – Griscelli syndrome; HPS – Hermansky‐Pudlak syndrome; KS – Kartagener syndrome (Primary ciliary dyskinesia); MVID – Microvillus inclusion disease; SEDT – Spondyloepiphyseal dysplasia tarda; SPG10 – Spastic paraplegia type 10; USH1B – Usher syndrome type 1B.
close

References

Akhmanova A and Hammer JA (2010) Linking molecular motors to membrane cargo. Current Opinion in Cell Biology 22: 479–487.

Andres DA , Seabra MC , Brown MS et al. (1993) cDNA cloning of component A of Rab geranylgeranyl transferase and demonstration of its role as a Rab escort protein. Cell 73: 1091–1099.

Antonny B , Madden D , Hamamoto S , Orci L and Schekman R (2001) Dynamics of the COPII coat with GTP and stable analogues. Nature Cell Biology 3: 531–537.

Arneson LN , Brickshawana A , Segovis CM et al. (2007) Cutting edge: Syntaxin 11 regulates lymphocyte‐mediated secretion and cytotoxicity. Journal of Immunology 179: 3397–3401.

Barrowman J , Bhandari D , Reinisch K and Ferro‐Novick S (2010) TRAPP complexes in membrane traffic: convergence through a common Rab. Nature Reviews. Molecular Cell Biology 11: 759–763.

BasuRay S , Mukherjee S , Romero EG , Seaman MNJ and Wandinger‐Ness A (2013) Rab7 mutants associated with Charcot‐Marie‐Tooth disease cause delayed growth factor receptor transport and altered endosomal and nuclear signaling. Journal of Biological Chemistry 288: 1135–1149.

Bi X , Corpina RA and Goldberg J (2002) Structure of the Sec23/24‐Sar1 pre‐budding complex of the COPII vesicle coat. Nature 419: 271–277.

Bi X , Mancias JD and Goldberg J (2007) Insights into COPII coat nucleation from the structure of Sec23.Sar1 complexed with the active fragment of Sec31. Developmental Cell 13: 635–645.

Boon M , Jorissen M , Proesmans M and De Boeck K (2013) Primary ciliary dyskinesia, an orphan disease. European Journal of Pediatrics 172: 151–162.

Boyadjiev SA , Fromme JC , Ben J et al. (2006) Cranio‐lenticulo‐sutural dysplasia is caused by a SEC23A mutation leading to abnormal endoplasmic‐reticulum‐to‐Golgi trafficking. Nature Genetics 38: 1192–1197.

Boyadjiev SA , Justice CM , Eyaid W et al. (2003) A novel dysmorphic syndrome with open calvarial sutures and sutural cataracts maps to chromosome 14q13‐q21. Human Genetics 113: 1–9.

Boyadjiev SA , Kim S‐D , Hata A et al. (2011) Cranio‐lenticulo‐sutural dysplasia associated with defects in collagen secretion. Clinical Genetics 80: 169–176.

Bush A , Cole P , Hariri M et al. (1998) Primary ciliary dyskinesia: diagnosis and standards of care. European Respiratory Journal 12: 982–988.

Cesaro S , Locatelli F , Lanino E et al. (2008) Hematopoietic stem cell transplantation for hemophagocytic lymphohistiocytosis: a retrospective analysis of data from the Italian Association of Pediatric Hematology Oncology (AIEOP). Haematologica 93: 1694–1701.

Cherry S , Jin EJ , Ozel MN et al. (2013) Charcot‐Marie‐Tooth 2B mutations in rab7 cause dosage‐dependent neurodegeneration due to partial loss of function. eLife 2: e01064.

Choi MY , Chan CCY , Chan D et al. (2009) Biochemical consequences of sedlin mutations that cause spondyloepiphyseal dysplasia tarda. Biochemical Journal 423: 233–242.

Chu B‐B , Ge L , Xie C et al. (2009) Requirement of myosin Vb.Rab11a.Rab11‐FIP2 complex in cholesterol‐regulated translocation of NPC1L1 to the cell surface. Journal of Biological Chemistry 284: 22481–22490.

Cullinane AR , Yeager C , Dorward H et al. (2014) Dysregulation of galectin‐3. Implications for hermansky‐pudlak syndrome pulmonary fibrosis. American Journal of Respiratory Cell and Molecular Biology 50: 1–613.

Dell'Angelica EC , Shotelersuk V , Aguilar RC , Gahl WA and Bonifacino JS (1999) Altered trafficking of lysosomal proteins in Hermansky‐Pudlak syndrome due to mutations in the beta 3A subunit of the AP‐3 adaptor. Molecular Cell 3: 11–21.

Di Pietro SM , Falcón‐Pérez JM , Tenza D et al. (2006) BLOC‐1 interacts with BLOC‐2 and the AP‐3 complex to facilitate protein trafficking on endosomes. Molecular Biology of the Cell 17: 4027–4038.

Donaldson JG and Jackson CL (2011) ARF family G proteins and their regulators: roles in membrane transport, development and disease. Nature Reviews. Molecular Cell Biology 12: 362–375.

Fartasch M (2004) The epidermal lamellar body: a fascinating secretory organelle. Journal of Investigative Dermatology 122: XI–XII.

Fisman DN (2000) Hemophagocytic syndromes and infection. Emerging Infectious Diseases 6: 601–608.

Fromme JC , Ravazzola M , Hamamoto S et al. (2007) The genetic basis of a craniofacial disease provides insight into COPII coat assembly. Developmental Cell 13: 623–634.

Fuchs‐Telem D , Stewart H , Rapaport D et al. (2011) CEDNIK syndrome results from loss‐of‐function mutations in SNAP29. British Journal of Dermatology 164: 610–616.

Gahl WA , Brantly M , Kaiser‐Kupfer MI et al. (1998) Genetic defects and clinical characteristics of patients with a form of oculocutaneous albinism (Hermansky‐Pudlak syndrome). New England Journal of Medicine 338: 1258–1264.

Gedeon AK , Colley A , Jamieson R et al. (1999) Identification of the gene (SEDL) causing X‐linked spondyloepiphyseal dysplasia tarda. Nature Genetics 22: 400–404.

Georges A , Bonneau J , Bonnefont‐Rousselot D et al. (2011) Molecular analysis and intestinal expression of SAR1 genes and proteins in Anderson's disease (Chylomicron retention disease). Orphanet Journal of Rare Diseases 6: 1.

Gerondopoulos A , Langemeyer L , Liang J‐R , Linford A and Barr FA (2012) BLOC‐3 mutated in Hermansky‐Pudlak syndrome is a Rab32/38 guanine nucleotide exchange factor. Current Biology: CB 22: 2135–2139.

Gibbs D , Diemer T , Khanobdee K et al. (2010) Function of MYO7A in the human RPE and the validity of shaker1 mice as a model for Usher syndrome 1B. Investigative Ophthalmology & Visual Science 51: 1130–1135.

Goizet C , Boukhris A , Mundwiller E et al. (2009) Complicated forms of autosomal dominant hereditary spastic paraplegia are frequent in SPG10. Human Mutation 30: E376–E385.

Hanon E , Stinchcombe JC , Saito M et al. (2000) Fratricide among CD8(+) T lymphocytes naturally infected with human T cell lymphotropic virus type I. Immunity 13: 657–664.

Hashimoto Y , Shirane M , Matsuzaki F et al. (2014) Protrudin Regulates Endoplasmic Reticulum Morphology and Function Associated with the Pathogenesis of Hereditary Spastic Paraplegia. Journal of Biological Chemistry 289: 12946–12961.

Huang M , Weissman JT , Beraud‐Dufour S et al. (2001) Crystal structure of Sar1‐GDP at 1.7 A resolution and the role of the NH2 terminus in ER export. Journal of Cell Biology 155: 937–948.

Huizing M , Sarangarajan R , Strovel E et al. (2001) AP‐3 mediates tyrosinase but not TRP‐1 trafficking in human melanocytes. Molecular Biology of the Cell 12: 2075–2085.

Hussain MM (2000) A proposed model for the assembly of chylomicrons. Atherosclerosis 148: 1–15.

Ishida‐Yamamoto A , Deraison C , Bonnart C et al. (2005) LEKTI is localized in lamellar granules, separated from KLK5 and KLK7, and is secreted in the extracellular spaces of the superficial stratum granulosum. Journal of Investigative Dermatology 124: 360–366.

Ishikura S , Klip A and Cell JP (2008) Muscle cells engage Rab8A and myosin Vb in insulin‐dependent GLUT4 translocation. American Journal of Physiology. Cell Physiology 295(4): C1016–C1025.

Jahn R and Scheller RH (2006) SNAREs – engines for membrane fusion. Nature Reviews. Molecular Cell Biology 7: 631–643.

Jaijo T , Aller E , Beneyto M et al. (2007) MYO7A mutation screening in Usher syndrome type I patients from diverse origins. Journal of Medical Genetics 44: e71.

Jones B , Jones EL , Bonney SA et al. (2003) Mutations in a Sar1 GTPase of COPII vesicles are associated with lipid absorption disorders. Nature Genetics 34: 29–31.

Kijima K , Numakura C , Izumino H et al. (2005) Mitochondrial GTPase mitofusin 2 mutation in Charcot‐Marie‐Tooth neuropathy type 2A. Human Genetics 116: 23–27.

Kim S‐D , Pahuja KB , Ravazzola M et al. (2012) The [corrected] SEC23‐SEC31 [corrected] interface plays critical role for export of procollagen from the endoplasmic reticulum. Journal of Biological Chemistry 287: 10134–10144.

Krämer EM , Schardt A and Nave KA (2001) Membrane traffic in myelinating oligodendrocytes. Microscopy Research and Technique 52: 656–671.

Levy E , Harmel E , Laville M et al. (2011) Expression of Sar1b enhances chylomicron assembly and key components of the coat protein complex II system driving vesicle budding. Arteriosclerosis, Thrombosis, and Vascular Biology 31: 2692–2699.

Marks MS , Heijnen HFG and Raposo G (2013) Lysosome‐related organelles: unusual compartments become mainstream. Current Opinion in Cell Biology 25: 495–505.

Meeths M , Bryceson YT , Rudd E et al. (2010) Clinical presentation of Griscelli syndrome type 2 and spectrum of RAB27A mutations. Pediatric Blood & Cancer 54: 563–572.

Ménager MM , Ménasché G , Romao M et al. (2007) Secretory cytotoxic granule maturation and exocytosis require the effector protein hMunc13‐4. Nature Immunology 8: 257–267.

Ménasché G , Ho CH , Sanal O et al. (2003) Griscelli syndrome restricted to hypopigmentation results from a melanophilin defect (GS3) or a MYO5A F‐exon deletion (GS1). Journal of Clinical Investigation 112: 450–456.

Ménasché G , Pastural E , Feldmann J et al. (2000) Mutations in RAB27A cause Griscelli syndrome associated with haemophagocytic syndrome. Nature Genetics 25: 173–176.

Millán JM , Aller E , Jaijo T et al. (2011) An update on the genetics of usher syndrome. Journal of Ophthalmology 2011: 417217.

Moore A , Escudier E , Roger G et al. (2006) RPGR is mutated in patients with a complex X linked phenotype combining primary ciliary dyskinesia and retinitis pigmentosa. Journal of Medical Genetics 43: 326–333.

Nakatani Y , Nakamura N , Sano J et al. (2000) Interstitial pneumonia in Hermansky‐Pudlak syndrome: significance of florid foamy swelling/degeneration (giant lamellar body degeneration) of type‐2 pneumocytes. Virchows Archiv: An International Journal of Pathology 437: 304–313.

Osanai K , Higuchi J , Oikawa R et al. (2010) Altered lung surfactant system in a Rab38‐deficient rat model of Hermansky‐Pudlak syndrome. American Journal of Physiology. Lung Cellular and Molecular Physiology 298: 243–251.

Peden AA , Oorschot V , Hesser BA et al. (2004) Localization of the AP‐3 adaptor complex defines a novel endosomal exit site for lysosomal membrane proteins. Journal of Cell Biology 164: 1065–1076.

Pennarun G , Escudier E , Chapelin C et al. (1999) Loss‐of‐function mutations in a human gene related to Chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia. American Journal of Human Genetics 65: 1508–1519.

Peretti N , Sassolas A , Roy CC et al. (2010) Guidelines for the diagnosis and management of chylomicron retention disease based on a review of the literature and the experience of two centers. Orphanet Journal of Rare Diseases 5: 24.

Rapaport D , Lugassy Y , Sprecher E and Horowitz M (2010) Loss of SNAP29 impairs endocytic recycling and cell motility. PloS One 5: e9759.

Reid E , Kloos M , Ashley‐Koch A et al. (2002) A kinesin heavy chain (KIF5A) mutation in hereditary spastic paraplegia (SPG10). American Journal of Human Genetics 71: 1189–1194.

Richmond B , Huizing M , Knapp J et al. (2005) Melanocytes derived from patients with Hermansky‐Pudlak Syndrome types 1, 2, and 3 have distinct defects in cargo trafficking. Journal of Investigative Dermatology 124: 420–427.

Robinson MS (2004) Adaptable adaptors for coated vesicles. Trends in Cell Biology 14: 167–174.

Ruemmele FM , Müller T , Schiefermeier N et al. (2010) Loss‐of‐function of MYO5B is the main cause of microvillus inclusion disease: 15 novel mutations and a CaCo‐2 RNAi cell model. Human Mutation 31: 544–551.

Schardt A , Brinkmann BG , Mitkovski M et al. (2009) The SNARE protein SNAP‐29 interacts with the GTPase Rab3A: Implications for membrane trafficking in myelinating glia. Journal of Neuroscience Research 87: 3465–3479.

Seixas E , Barros M , Seabra MC and Barral DC (2013) Rab and Arf Proteins in Genetic Diseases. Traffic 14: 871–885.

Setty SRG , Tenza D , Sviderskaya EV et al. (2008) Cell‐specific ATP7A transport sustains copper‐dependent tyrosinase activity in melanosomes. Nature 454: 1142–1146.

Siddiqi SA , Gorelick FS , Mahan JT and Mansbach CM (2003) COPII proteins are required for Golgi fusion but not for endoplasmic reticulum budding of the pre‐chylomicron transport vesicle. Journal of Cell Science 116: 415–427.

Sprecher E , Ishida‐Yamamoto A , Mizrahi‐Koren M et al. (2005) A mutation in SNAP29, coding for a SNARE protein involved in intracellular trafficking, causes a novel neurocutaneous syndrome characterized by cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma. American Journal of Human Genetics 77: 242–251.

Stenmark H (2009) Rab GTPases as coordinators of vesicle traffic. Nature Reviews. Molecular Cell Biology 10: 513–525.

Talmon G , Holzapfel M , DiMaio DJ and Muirhead D (2012) Rab11 is a useful tool for the diagnosis of microvillous inclusion disease. International Journal of Surgical Pathology 20: 252–256.

Thoeni CE , Vogel GF , Tancevski I et al. (2014) Microvillus inclusion disease: loss of Myosin vb disrupts intracellular traffic and cell polarity. Traffic (Copenhagen, Denmark) 15: 22–42.

Tiller GE , Hannig VL , Dozier D et al. (2001) A recurrent RNA‐splicing mutation in the SEDL gene causes X‐linked spondyloepiphyseal dysplasia tarda. American Journal of Human Genetics 68: 1398–1407.

Trybus KM (2008) Myosin V from head to tail. Cellular and Molecular Life Sciences: CMLS 65: 1378–1389.

Vacca B , Bazellières E , Nouar R et al. (2014) Drebrin E depletion in human intestinal epithelial cells mimics Rab8a loss of function. Human Molecular Genetics 23: 2834–2846.

Van Gele M , Dynoodt P and Lambert J (2009) Griscelli syndrome: a model system to study vesicular trafficking. Pigment Cell & Melanoma Research 22: 268–282.

Venditti R , Scanu T , Santoro M et al. (2012) Sedlin controls the ER export of procollagen by regulating the Sar1 cycle. Science (New York, N.Y.) 337: 1668–1672.

Voskoboinik I and Trapani JA (2013) Perforinopathy: a spectrum of human immune disease caused by defective perforin delivery or function. Frontiers in Immunology 4: 441.

Wang D , Chan C‐C , Cherry S and Hiesinger PR (2013) Membrane trafficking in neuronal maintenance and degeneration. Cellular and Molecular Life Sciences: CMLS 70: 2919–2934.

Wei ML (2006) Hermansky‐Pudlak syndrome: a disease of protein trafficking and organelle function. Pigment Cell Research/Sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society 19: 19–42.

Westbroek W , Klar A , Cullinane AR et al. (2012) Cellular and clinical report of new Griscelli syndrome type III cases. Pigment Cell & Melanoma Research 25: 47–56.

Westbroek W , Lambert J , Bahadoran P et al. (2003) Interactions of human Myosin Va isoforms, endogenously expressed in human melanocytes, are tightly regulated by the tail domain. Journal of Investigative Dermatology 120: 465–475.

Whyte MP , Gottesman GS , Eddy MC and McAlister WH (1999) X‐linked recessive spondyloepiphyseal dysplasia tarda. Clinical and radiographic evolution in a 6‐generation kindred and review of the literature. Medicine 78: 9–25.

Wong SH , Xu Y , Zhang T et al. (1999) GS32, a novel Golgi SNARE of 32 kDa, interacts preferentially with syntaxin 6. Molecular Biology of the Cell 10: 119–134.

Zhao C , Takita J , Tanaka Y et al. (2001) Charcot‐Marie‐Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell 105: 587–597.

Zur Stadt U , Rohr J , Seifert W et al. (2009) Familial hemophagocytic lymphohistiocytosis type 5 (FHL‐5) is caused by mutations in Munc18‐2 and impaired binding to syntaxin 11. American Journal of Human Genetics 85: 482–492.

Zur Stadt U , Schmidt S , Kasper B et al. (2005) Linkage of familial hemophagocytic lymphohistiocytosis (FHL) type‐4 to chromosome 6q24 and identification of mutations in syntaxin 11. Human Molecular Genetics 14: 827–834.

Further Reading

Aridor M and Hannan LA (2000) Traffic jam: a compendium of human diseases that affect intracellular transport processes. Traffic (Copenhagen, Denmark) 1: 836–851.

Aridor M and Hannan LA (2002) Traffic jams II: an update of diseases of intracellular transport. Traffic (Copenhagen, Denmark) 3: 781–790.

Bucci C , Bakke O and Progida C (2012) Charcot‐Marie‐Tooth disease and intracellular traffic. Progress in Neurobiology 99: 191–225.

Garcia‐Gonzalo FR and Reiter JF (2012) Scoring a backstage pass: mechanisms of ciliogenesis and ciliary access. Journal of Cell Biology 197: 697–709.

Gentil BJ and Cooper L (2012) Molecular basis of axonal dysfunction and traffic impairments in CMT. Brain Research Bulletin 88: 444–453.

Howell GJ , Holloway ZG , Cobbold C , Monaco AP and Ponnambalam S (2006) Cell biology of membrane trafficking in human disease. International Review of Cytology 252: 1–69.

Hutagalung AH and Novick PJ (2011) Role of Rab GTPases in membrane traffic and cell physiology. Physiological Reviews 91: 119–149.

Krzewski K and Cullinane AR (2013) Evidence for defective Rab GTPase‐dependent cargo traffic in immune disorders. Experimental Cell Research 319: 2360–2367.

Olkkonen VM and Ikonen E (2006) When intracellular logistics fails – genetic defects in membrane trafficking. Journal of Cell Science 119: 5031–5045.

Related Sub-Topics:

Mutational Mechanisms of Genetic Disease | Specific Genetic Disorders | Cell Cytoskeleton | Cell Compartments and Cellular Organelles | Cellular Transport | Cell Membranes
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Membrane Traffic and Disease
 
How to Cite close
Cláudio, Nuno, Pereira, Francisco JC, and Barral, Duarte C(Nov 2014) Membrane Traffic and Disease. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0020892]