Modulation of the actin cytoskeleton via gelsolin regulates aacuolar H+-ATPase recycling
Da Silva, Nicolas
Brown, Christopher R.
Smith, Peter J. S.
MetadataShow full item record
The role of the actin cytoskeleton in regulating membrane protein trafficking is complex and depends on the cell type and protein being examined. Using the epididymis as a model system in which luminal acidification is crucial for sperm maturation and storage, we now report that modulation of the actin cytoskeleton by the calcium-activated actin-capping and -severing protein gelsolin plays a key role in regulating vacuolar H+-ATPase (V-ATPase) recycling. Epididymal clear cells contain abundant V-ATPase in their apical pole, and an increase in their cell-surface V-ATPase expression correlates with an increase in luminal proton secretion. We have shown that apical membrane accumulation of V-ATPase is triggered by an elevation in cAMP following activation of bicarbonate-regulated soluble adenylyl cyclase in response to alkaline luminal pH (Pastor-Soler, N., Beaulieu, V., Litvin, T. N., Da Silva, N., Chen, Y., Brown, D., Buck, J., Levin, L. R., and Breton, S. (2003) J. Biol. Chem. 278, 49523-49529). Here, we show that clear cells express high levels of gelsolin, indicating a potential role in the functional activity of these cells. When jasplakinolide was used to overcome the severing action of gelsolin by polymerizing actin, complete inhibition of the alkaline pH- and cAMP-induced apical membrane accumulation of V-ATPase was observed. Conversely, when gelsolin-mediated actin filament elongation was inhibited using a 10-residue peptide (PBP10) derived from the phosphatidylinositol 4,5-bisphosphate-binding region (phosphoinositide-binding domain 2) of gelsolin, significant V-ATPase apical membrane mobilization was induced, even at acidic luminal pH. In contrast, the calcium chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis(acetoxymethyl ester) and the phospholipase C inhibitor U-73122 inhibited the alkaline pH-induced V-ATPase apical accumulation. Thus, maintenance of the actin cytoskeleton in a depolymerized state by gelsolin facilitates calcium-dependent apical accumulation of V-ATPase in response to luminal pH alkalinization. Gelsolin is present in other cell types that express the V-ATPase in their plasma membrane and recycling vesicles, including kidney intercalated cells and osteoclasts. Therefore, modulation of the actin cortex by this severing and capping protein may represent a common mechanism by which these cells regulate their rate of proton secretion.
Author Posting. © American Society for Biochemistry and Molecular Biology, 2005. This article is posted here by permission of American Society for Biochemistry and Molecular Biology for personal use, not for redistribution. The definitive version was published in Journal of Biological Chemistry 280 (2005): 8452-8463, doi:10.1074/jbc.M412750200.
Showing items related by title, author, creator and subject.
Morfini, Gerardo A.; Bosco, Daryl A.; Brown, Hannah; Gatto, Rodolfo; Kaminska, Agnieszka; Song, Yuyu; Molla, Linda; Baker, Lisa; Marangoni, M. Natalia; Berth, Sarah; Tavassoli, Ehsan; Bagnato, Carolina; Tiwari, Ashutosh; Hayward, Lawrence J.; Pigino, Gustavo F.; Watterson, D. Martin; Huang, Chun-Fang; Banker, Gary; Brown, Robert H.; Brady, Scott T. (Public Library of Sceince, 2013-06-12)Dying-back degeneration of motor neuron axons represents an established feature of familial amyotrophic lateral sclerosis (FALS) associated with superoxide dismutase 1 (SOD1) mutations, but axon-autonomous effects of ...
Arp2/3 complex inhibition radically alters lamellipodial actin architecture, suspended cell shape, and the cell spreading process Henson, John H.; Yeterian, Mesrob; Weeks, Richard M.; Medrano, Angela E.; Brown, Briana L.; Geist, Heather L.; Pais, Mollyann D.; Oldenbourg, Rudolf; Shuster, Charles B. (American Society for Cell Biology, 2015-01-07)Recent studies have investigated the dendritic actin cytoskeleton of the cell edge's lamellipodial (LP) region by experimentally decreasing the activity of the actin filament nucleator and branch former, the Arp2/3 complex. ...
Ages and magnetic structures of the South China Sea constrained by deep tow magnetic surveys and IODP Expedition 349 Li, Chun-Feng; Xu, Xing; Lin, Jian; Sun, Zhen; Zhu, Jian; Yao, Yongjian; Zhao, Xixi; Liu, Qingsong; Kulhanek, Denise K.; Wang, Jian; Song, Taoran; Zhao, Junfeng; Qiu, Ning; Guan, Yongxian; Zhou, Zhiyuan; Williams, Trevor; Bao, Rui; Briais, Anne; Brown, Elizabeth A.; Chen, Yifeng; Clift, Peter D.; Colwell, Frederick S.; Dadd, Kelsie A.; Ding, Weiwei; Almeida, Ivan Hernandez; Huang, Xiao-Long; Hyun, Sangmin; Jiang, Tao; Koppers, Anthony A. P.; Li, Qianyu; Liu, Chuanlian; Liu, Zhifei; Nagai, Renata H.; Peleo-Alampay, Alyssa; Su, Xin; Tejada, Maria Luisa G.; Trinh, Hai Son; Yeh, Yi-Ching; Zhang, Chuanlun; Zhang, Fan; Zhang, Guo-Liang (John Wiley & Sons, 2014-12-27)Combined analyses of deep tow magnetic anomalies and International Ocean Discovery Program Expedition 349 cores show that initial seafloor spreading started around 33 Ma in the northeastern South China Sea (SCS), but varied ...