FIGURE 9:

Shear induces vacuole formation via a noncanonical autophagic pathway. Microvilli on the apical side of relatively immature epithelial cells are formed by a CDHR2-dependent clustering mechanism. Shear stress on loosely packed and motile microvilli stimulates the autophagy machinery in a noncanonical pathway that is distinct from Beclin-dependent canonical autophagy. This noncanonical process triggers distinct trafficking events originating from the endoplasmic reticulum that are modulated differently by the small molecule inhibitors CQ and BafA, resulting in the formation of large LC3 and LAMP1-decorated degradative vacuoles.