Article Text
Abstract
Many cellular functions depend on the correct delivery of proteins to specific intracellular destinations. Mutations that alter protein structure and disrupt trafficking of the protein (the “cargo”) occur in many genetic disorders. In addition, an increasing number of disorders have been linked to mutations in the genes encoding components of the vesicular transport machinery responsible for normal protein trafficking. We review the clinical phenotypes and molecular pathology of such inherited “protein-trafficking disorders”, which provide seminal insights into the molecular mechanisms of protein trafficking. Further characterisation of this expanding group of disorders will provide a basis for developing new diagnostic techniques and treatment strategies and offer insights into the molecular pathology of common multifactorial diseases that have been linked to disordered trafficking mechanisms.
- AD, Alzheimer disease
- AP, adaptor protein
- APP, amyloid precursor protein
- ARC, arthrogryposis, renal dysfunction and cholestasis syndrome
- BLOC, biogenesis of lysosome-related organelle complex
- CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma
- CMT, Charcot–Marie–Tooth
- COP, coat protein
- ER, endoplasmic reticulum
- ERGIC, ER–Golgi intermediate compartment
- GS, Griscelli syndrome
- GTPase, guanine triphosphatase
- HOPS, homotypic fusion and vacuolar protein sorting
- HPS, Hermansky–Pudlak syndrome
- HS, haemophagocytic syndrome
- HSP, hereditary spastic paraplegia
- IDT, inherited disorders of trafficking
- LAMP, lysosome-associated membrane protein
- LRO, lysosome-related organelle
- OMIM, Online Mendelian Inheritance in Man
- SCA5, spinocerebellar ataxia type 5
- SNARE, soluble N-ethylmaleimide-sensitive fusion attachment protein receptor
- TGN, trans-Golgi network
- VAMP, vesicle-associated membrane protein
- inherited trafficking disorders
- vesicular trafficking
- intracellular protein trafficking
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- AD, Alzheimer disease
- AP, adaptor protein
- APP, amyloid precursor protein
- ARC, arthrogryposis, renal dysfunction and cholestasis syndrome
- BLOC, biogenesis of lysosome-related organelle complex
- CEDNIK (cerebral dysgenesis, neuropathy, ichthyosis, and palmoplantar keratoderma
- CMT, Charcot–Marie–Tooth
- COP, coat protein
- ER, endoplasmic reticulum
- ERGIC, ER–Golgi intermediate compartment
- GS, Griscelli syndrome
- GTPase, guanine triphosphatase
- HOPS, homotypic fusion and vacuolar protein sorting
- HPS, Hermansky–Pudlak syndrome
- HS, haemophagocytic syndrome
- HSP, hereditary spastic paraplegia
- IDT, inherited disorders of trafficking
- LAMP, lysosome-associated membrane protein
- LRO, lysosome-related organelle
- OMIM, Online Mendelian Inheritance in Man
- SCA5, spinocerebellar ataxia type 5
- SNARE, soluble N-ethylmaleimide-sensitive fusion attachment protein receptor
- TGN, trans-Golgi network
- VAMP, vesicle-associated membrane protein
Footnotes
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Published Online First 25 May 2007
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Funding: PG is a GSK Clinician Scientist.
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Competing interests: None declared.