Caspase remodeling of the spectrin membrane skeleton during lens development and aging

Terminal differentiation of lens fiber cells resembles the apoptotic proces s in that organelles are lost, DNA is fragmented, and changes in membrane m orphology occur. However, unlike classically apoptotic cells, which are dis integrated by membrane blebbing and vesiculation, aging lens fiber cells ar e compressed into the center of the lens, where they undergo cell-cell fusi on and the formation of specialized membrane interdigitations. In classical ly apoptotic cells, caspase cleavage of the cytoskeletal protein alpha -spe ctrin to similar to 150-kDa fragments is believed to be important for membr ane blebbing, We report that caspase(s) cleave alpha -spectrin to similar t o 150-kDa fragments and beta -spectrin to similar to 120- and similar to 80 -kDa fragments during late embryonic chick lens development. These fragment s continue to accumulate with age so that in the oldest fiber cells of the adult lens, most, if not all, of the spectrin is cleaved to discrete fragme nts. Thus, unlike classical apoptosis, where caspase-cleaved spectrin is sh ort lived, lens fiber cells contain spectrin fragments that appear to be st able for the lifetime of the organism. Moreover, fragmentation of spectrin results in reduced membrane association and thus may lead to permanent remo deling of the membrane skeleton. Partial and specific proteolysis of membra ne skeleton components by caspases may be important for age-related membran e changes in the lens.