Role of Band 3 in Homeostasis and Cell Shape

The most surprising result of both of these studies is Harvard University that animals can survive to adulthood in the absence Cambridge, Massachusetts 02138 of band 3. They suffer from chronic hemolytic anemia (severe for mice, moderate for cattle) resulting in high Two important functions of membrane proteins are to rates of neonatal death (higher for mice than cattle). The regulate the internal cellular environment and to deter-adult mice examined showed a high rate of hema-mine cell shape. How membrane proteins regulate ho-topoesis which may be a compensatory mechanism for meostasis in the cell and throughout the whole organism the mice to survive. To address the relative importance is a fundamental question of cellular physiology. How of anion exchange and cytoskeletal binding, future work membrane proteins anchor the cytoskeleton to regulate should include experiments using transgenes that en-cell morphology remains a question of keen interest. The code either the membrane domain or cytoplasmic do-investigation of the erythrocyte anion exchange protein, main to rescue the observed phenotypes. band 3 (also called AE1) has been at the center of these CO 2 and pH Regulation two questions for the last several decades (reviewed in Both studies showed that stilbene disulfonate-inhibit-Jay and Cantley, 1986; Tanner, 1993). Recent studies able anion exchange was almost completely absent. by Peters et al. (in this issue) and by Inaba et al. (1996) Whether there is a stringent requirement for anion ex-have addressed the importance of band 3 in homeosta-change in eythrocytes remains an open question. AE2 sis and cell shape. A third study by Sekler et al. (in this and AE3 did not increase in band 3 Ϫ murine red blood issue) implicates the homologous nonerythroid anion cells, but other anion exchangers were not examined. exchanger AE2 in a particular role in pH regulation. Neither group measured total CO 2 in erythrocytes which Band 3 Band 3, a 95 kDa integral membrane protein, was extensively characterized in early investigations of membrane proteins because it is very abundant (1.2 ϫ 10 6 copies per cell) and easily purified (Fairbanks et al., 1971). Its biochemical and biophysical characterization (reviewed in Jay and Cantley, 1986) coupled with the early determination of its sequence (Kopito and Lodish, 1985) have made band 3 an excellent model for studying membrane protein structure and function. There are two putative functions of band 3: anion exchange is carried out by the multi-spanning integral membrane domain …