Model for function and formation/closure of nanoholes. (A) Schematic of possible mechanisms for nanohole formation. Top view of ER sheet with a dashed gray line indicating the region shown as a side profile below. Nanohole formation by loops that shrink (left) and/or fusion of membrane sheets across the ER lumen, generated or stabilized by reticulons. (B) Schematic of possible mechanisms for nanohole closure. Diffusion of curvature-stabilizing proteins to sheet edge and subsequent tubule extension (left). Region marked by dashed red box is displayed as a tilted 3D structure to show that when nanoholes approach the edges of a sheet, the curved edge of a nanohole will be directly adjacent to the curved sheet edge. Potential mechanism of nanohole closure by fission machinery (right). (C) Schematic of geometries used to model the ER for nanohole function in tubule extension. (D) Plot of curved fraction of surface area as number of holes and tubule length are varied with the total surface area held constant. (E) Three points on the red isocline in D, coordinates marked with square, triangle, and circle, are drawn to scale with the appropriate number of holes and length of tubule.