title: Effect of acid maltase deficiency on the endosomal/lysosomal system and glucose transporter 4.
abstract: Membrane bound glycogen storage in muscle is characteristic for the lysosomal storage disorder acid maltase (acid alpha-glucosidase) deficiency while in phosphofructokinase and phosphorylase deficiency, glycogen is stored free in the cytoplasm. Using immunohistochemistry, we examined whether acid maltase deficiency had an effect on early endosomes, recycling endosomes and trans-Golgi network, vesicle systems linked to lysosomes. Vacuolated glycogen containing fibres stained intensely for the lysosomal marker lysosomal-membrane-protein-1 within fibres and at the sarcolemma. There was a similar increase in immunoreactivity for markers of early endosomes (rab5), recycling endosomes (transferrin receptor) and the trans-Golgi network. In acid maltase deficiency, but not in normal muscle or other glycogenoses, staining for the insulin responsive glucose transporter 4 was markedly increased and partially co-localised with all vesicular markers. Our results suggest an effect of acid maltase deficiency extending to various vesicle systems linked to lysosomes. The enzyme defect may also affect the homoeostasis of receptors cycling through these organelles such as glucose transporter 4.
authors.affiliation: University Department of Clinical Neuroscience, Royal Free and University College Medical School, London, UK. m.orth@ion.ucl.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Orth
authors.forename: R R
authors.initials: RR
authors.lastname: Mundegar
mesh_terms: D000328:Adult; D001706:Biopsy; D011992:Endosomes / Q000378:metabolism*; D005087:Glucan 1,4-alpha-Glucosidase / Q000172:deficiency* / Q000502:physiology; D051275:Glucose Transporter Type 4; D006008:Glycogen Storage Disease / Q000201:enzymology / Q000473:pathology; D006009:Glycogen Storage Disease Type II / Q000378:metabolism* / Q000473:pathology; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008247:Lysosomes / Q000378:metabolism*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D009132:Muscles / Q000201:enzymology / Q000473:pathology; D000520:alpha-Glucosidases
chemical_list: D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; C495692:SLC2A4 protein, human; D000520:alpha-Glucosidases; D005087:Glucan 1,4-alpha-Glucosidase