Mucolipin Co-deficiency Causes Accelerated Endolysosomal Vacuolation of Enterocytes and Failure-to-Thrive from Birth to Weaning

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Intestinal digestion is very different before and after weaning. In adults, extracellular enzymes in the lumen of digestive tract digest proteins and the enterocytes lining the intestine absorb the resulting amino acids. During suckling, proteins reach the intestinal lumen intact, are taken (endocytosed) by enterocytes and degraded inside them. For this intracellular digestion enterocytes prior to weaning have specialized lysosomes with digestive enzymes. Lysosomes are also of biomedical relevance because their partial dysfunction causes ∼50 genetic disorders with a range of symptoms (Lysosomal Storage Disorders; LSDs). We found that enterocytes prior to weaning express two related proteins implicated in certain LSDs (mucolipins 1 and 3) and that their co-absence causes pathological vacuolation of enterocytes, diminished apical endocytosis from the intestinal lumen, diarrhea and delayed growth (failure to thrive) from birth to weaning. Our results implicate lysosomes in neonatal intestinal disorders, a major cause of infant mortality, and suggest transient intestinal dysfunction might affect newborns with LSDs. Hence, we link two large sets of disorders that are presently considered and treated as unrelated. Finally, we propose that the special mechanisms for the uptake and digestion of maternal milk are not unique to mammals, as embryos of oviparous species use a similar mechanism for the digestion of maternally-provided yolk.

Vyšlo v časopise: Mucolipin Co-deficiency Causes Accelerated Endolysosomal Vacuolation of Enterocytes and Failure-to-Thrive from Birth to Weaning. PLoS Genet 10(12): e32767. doi:10.1371/journal.pgen.1004833
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004833

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