TRPML1’s Impact on MLIV
In the article, “Fusion of lysosomes with secretory organelles leads to uncontrolled exocytosis in the lysosomal storage disease mucolipidosis type IV” discussed the impacts of TRMPL1 on MLIV. Lysosomes are important in maintaining healthy cells, however, with the absence of lysosomal TRP channel TRPML1 then the lysosomal pH becomes more acidic because of the calcium leakage; hence, this makes lysosomes more sensitive to fusing, and due to being near exocytosis regulating secretory granules in polarized secretory cells, phagocytosis occurs between the two organelles to create a larger organelle. This enlargement fusion and absence of TRPML1 cause lysosomal storage disease (LSD) Mucolipidosis type IV (MLIV). MLIV is an inherited LSD that is known for causing neurodegenerative disorders with corneal opacity, achlorhydria, and impaired neuromuscular junctions which causes skeletal muscles to waste and …show more content…
TRPML1 is a nonselective calcium-permeable cation channel that is activated via endolysosomal lipid PI(3,5)P2. TRPML1 helps regulate lysosomal pH and releasement of lysosomal calcium; although the full extent to its functions and how and when it causes the MLIV are still unknown. This is because past studies focused on constitutive membrane trafficking to and from lysosomes since MLIV patients had cytoplasmic buildup of inclusion bodies with multiple lamellar membranes and storage of lipids and proteins (Park et al., 2016). However, membrane trafficking did not explain impaired neuromuscular and secretory cells’ functions regulate exocytosis since trafficking takes minutes to hours while exocytosis takes milliseconds to perform. Hence, the researchers did an experiment using mouse models with MLIV and NPC1 (Niemann-Pick type C1) to observe several forms of exocytosis
In the article, “Fusion of lysosomes with secretory organelles leads to uncontrolled exocytosis in the lysosomal storage disease mucolipidosis type IV” discussed the impacts of TRMPL1 on MLIV. Lysosomes are important in maintaining healthy cells, however, with the absence of lysosomal TRP channel TRPML1 then the lysosomal pH becomes more acidic because of the calcium leakage; hence, this makes lysosomes more sensitive to fusing, and due to being near exocytosis regulating secretory granules in polarized secretory cells, phagocytosis occurs between the two organelles to create a larger organelle. This enlargement fusion and absence of TRPML1 cause lysosomal storage disease (LSD) Mucolipidosis type IV (MLIV). MLIV is an inherited LSD that is known for causing neurodegenerative disorders with corneal opacity, achlorhydria, and impaired neuromuscular junctions which causes skeletal muscles to waste and …show more content…
TRPML1 is a nonselective calcium-permeable cation channel that is activated via endolysosomal lipid PI(3,5)P2. TRPML1 helps regulate lysosomal pH and releasement of lysosomal calcium; although the full extent to its functions and how and when it causes the MLIV are still unknown. This is because past studies focused on constitutive membrane trafficking to and from lysosomes since MLIV patients had cytoplasmic buildup of inclusion bodies with multiple lamellar membranes and storage of lipids and proteins (Park et al., 2016). However, membrane trafficking did not explain impaired neuromuscular and secretory cells’ functions regulate exocytosis since trafficking takes minutes to hours while exocytosis takes milliseconds to perform. Hence, the researchers did an experiment using mouse models with MLIV and NPC1 (Niemann-Pick type C1) to observe several forms of exocytosis