Cation‐Dependent Mannose 6‐Phosphate Receptor: Tag, You're it!

Approximately 50 different lysosomal storage disorders affect one in every 5000 births, limiting life expectancy and quality of life. Therapies are available for a handful of these disorders. Sixty different lysosomal enzymes are responsible for recycling macromolecules in cells. In normal functioning cells, lysosomal enzymes are synthesized in the endoplasmic reticulum and are transported to the lysosome. Transportation of lysosomal enzymes occurs when a mannose 6‐phosphate (Man‐6‐P) tag is placed on these enzymes, which is recognized by the cation‐dependent mannose‐6‐phophate receptor (CD‐MPR). The CD‐MPR binds to the Man‐6‐P tags through a recognition site (Y45, Q66, H105, R111, E133, R135, Y143) and transports the enzymes from the Golgi apparatus to an endosome where enzymes are released from CD‐MPR due to a more acidic environment. Enzymes are finally transported via vesicles to the lysosome to accomplish their function. Without the Man‐6‐P tags, CD‐MPR cannot bind to the enzymes, prohibiting transportation to an endosome and ultimately the lysosome. If lysosomal enzymes are not properly transported, they are secreted out of the cell, causing lysosomal storage disorders due to buildup of macromolecules in the lysosome. The Brown Deer SMART Team (Students Modeling A Research Topic) created a physical model of CD‐MPR using 3D printing technology. Supported by grants from NIH‐NCRR‐SEPA and NIH‐CTSA.