Changes in lysosome shape and distribution correlated with changes in cytoplasmic pH

doi:10.1083/jcb.108.3.855

This Article

	Full Text (PDF, 2813K)
	Alert me when this article is cited
	Citation Map

Services

	Email this article
	Similar articles in this journal
	Similar articles in PubMed
	Alert me to new content in the JCB
	Download to citation manager

Citing Articles

	Citing Articles via HighWire
	Citing Articles via CrossRef
	Citing Articles via Google Scholar

Google Scholar

	Articles by Heuser, J.
	Search for Related Content

PubMed

	PubMed Citation
	Articles by Heuser, J.


Social Bookmarking

	What's this?

ARTICLES

Changes in lysosome shape and distribution correlated with changes in cytoplasmic pH

J Heuser
Washington University School of Medicine, St. Louis, Missouri 63110.

Lysosomes labeled by uptake of extracellular horseradish peroxidase display remarkable changes in shape and cellular distribution when cytoplasmic pH is experimentally altered. Normally, lysosomes in macrophages and fibroblasts cluster around the cell center. However, when the cytoplasmic pH is lowered to approximately pH 6.5 by applying acetate or by various other means, lysosomes promptly move outward and accumulate in tight clusters at the very edge of the cell, particularly in regions that are actively ruffling before acidification but become quiescent. This movement follows the distribution of microtubules in these cells, and does not occur if microtubules are depolymerized with nocodazole before acidification. Subsequent removal of acetate or the other stimuli to acidification results in prompt resumption of ruffling activity and return of lysosomes into a tight cluster at the cell center. This is correlated with a rebound alkalinization of the cytoplasm. Correspondingly, direct application of weak bases also causes hyperruffling and unusually complete withdrawal of lysosomes to the cell center. Thus, lysosomes appear to be acted upon by microtubule- based motors of both the anterograde (kinesin) type as well as the retrograde (dynein) type, or else they possess bidirectional motors that are reversed by changes in cytoplasmic pH. During the outward movements induced by acidification, lysosomes also appear to be smaller and more predominantly vesicular than normal, while during inward movements they appear to be more confluent and elongated than normal, often becoming even more tubular than in phorbol-treated macrophages (Phaire-Washington, L., S. C. Silverstein, and E. Wang. 1980. J. Cell Biol. 86:641-655). These size and shape changes suggest that cytoplasmic pH also affects the fusion/fission properties of lysosomes. Combined with pH effects on their movement, the net result during recovery from acidification is a stretching of lysosomes into tubular forms along microtubules.
Add to CiteULike CiteULike Add to Complore Complore Add to Connotea Connotea Add to Del.icio.us Del.icio.us Add to Digg Digg Facebook Add to Reddit Reddit Add to Technorati Technorati Twitter What's this?

This article has been cited by other articles:

Yoshizaki, M., Tazawa, A., Kasumi, E., Sasawatari, S., Itoh, K., Dohi, T., Sasazuki, T., Inaba, K., Makrigiannis, A. P., Toyama-Sorimachi, N. (2009). Spatiotemporal regulation of intracellular trafficking of Toll-like receptor 9 by an inhibitory receptor, Ly49Q. Blood 114: 1518-1527 [Abstract] [Full Text]
Nabavi, N., Urukova, Y., Cardelli, M., Aubin, J. E., Harrison, R. E. (2008). Lysosome Dispersion in Osteoblasts Accommodates Enhanced Collagen Production during Differentiation. J. Biol. Chem. 283: 19678-19690 [Abstract] [Full Text]
Hirokawa, N., Noda, Y. (2008). Intracellular Transport and Kinesin Superfamily Proteins, KIFs: Structure, Function, and Dynamics. Physiol. Rev. 88: 1089-1118 [Abstract] [Full Text]
Deneka, M., Pelchen-Matthews, A., Byland, R., Ruiz-Mateos, E., Marsh, M. (2007). In macrophages, HIV-1 assembles into an intracellular plasma membrane domain containing the tetraspanins CD81, CD9, and CD53. JCB 177: 329-341 [Abstract] [Full Text]
Kim, H.-S., Takahashi, M., Matsuo, K., Ono, Y. (2007). Recruitment of CG-NAP to the Golgi apparatus through interaction with dynein-dynactin complex. GENES CELLS 12: 421-434 [Abstract] [Full Text]
Zhao, Y., Gaidarov, I., Keen, J. H. (2007). Phosphoinositide 3-Kinase C2{alpha} Links Clathrin to Microtubule-dependent Movement. J. Biol. Chem. 282: 1249-1256 [Abstract] [Full Text]
Pardo, J. M., Cubero, B., Leidi, E. O., Quintero, F. J. (2006). Alkali cation exchangers: roles in cellular homeostasis and stress tolerance. J Exp Bot 57: 1181-1199 [Abstract] [Full Text]
Brett, C. L., Tukaye, D. N., Mukherjee, S., Rao, R. (2005). The Yeast Endosomal Na+(K+)/H+ Exchanger Nhx1 Regulates Cellular pH to Control Vesicle Trafficking. Mol. Biol. Cell 16: 1396-1405 [Abstract] [Full Text]
Ro, H.-a., Carson, J. H. (2004). pH Microdomains in Oligodendrocytes. J. Biol. Chem. 279: 37115-37123 [Abstract] [Full Text]
Carini, R., Castino, R., De Cesaris, M. G., Splendore, R., Demoz, M., Albano, E., Isidoro, C. (2004). Preconditioning-induced cytoprotection in hepatocytes requires Ca2+-dependent exocytosis of lysosomes. J. Cell Sci. 117: 1065-1077 [Abstract] [Full Text]
Yeaman, C., Grindstaff, K. K., Nelson, W. J. (2004). Mechanism of recruiting Sec6/8 (exocyst) complex to the apical junctional complex during polarization of epithelial cells. J. Cell Sci. 117: 559-570 [Abstract] [Full Text]
Cao, H., Orth, J. D., Chen, J., Weller, S. G., Heuser, J. E., McNiven, M. A. (2003). Cortactin Is a Component of Clathrin-Coated Pits and Participates in Receptor-Mediated Endocytosis. Mol. Cell. Biol. 23: 2162-2170 [Abstract] [Full Text]
Andrews, N. W. (2002). Lysosomes and the plasma membrane: trypanosomes reveal a secret relationship. JCB 158: 389-394 [Abstract] [Full Text]
Tapper, H., Furuya, W., Grinstein, S. (2002). Localized Exocytosis of Primary (Lysosomal) Granules During Phagocytosis: Role of Ca2+-Dependent Tyrosine Phosphorylation and Microtubules. J. Immunol. 168: 5287-5296 [Abstract] [Full Text]
Plitz, T., Pfeffer, K. (2001). Intact Lysosome Transport and Phagosome Function Despite Kinectin Deficiency. Mol. Cell. Biol. 21: 6044-6055 [Abstract] [Full Text]
Figueroa-Arredondo, P., Heuser, J. E., Akopyants, N. S., Morisaki, J. H., Giono-Cerezo, S., Enriquez-Rincon, F., Berg, D. E. (2001). Cell Vacuolation Caused by Vibrio cholerae Hemolysin. Infect. Immun. 69: 1613-1624 [Abstract] [Full Text]
Bendayan, M., Gisiger, V. (2001). Demonstration of Acetylcholinesterase Molecular Forms in a Continuous Tubular Lysosomal System of Rat Pancreatic Acinar Cells. J. Histochem. Cytochem. 49: 29-40 [Abstract] [Full Text]
Caler, E. V., Morty, R. E., Burleigh, B. A., Andrews, N. W. (2000). Dual Role of Signaling Pathways Leading to Ca2+ and Cyclic AMP Elevation in Host Cell Invasion by Trypanosoma cruzi. Infect. Immun. 68: 6602-6610 [Abstract] [Full Text]
Reese, E. L., Haimo, L. T. (2000). Dynein, Dynactin, and Kinesin II's Interaction with Microtubules Is Regulated during Bidirectional Organelle Transport. JCB 151: 155-166 [Abstract] [Full Text]
Vitale, N., Ferrans, V. J., Moss, J., Vaughan, M. (2000). Identification of Lysosomal and Golgi Localization Signals in GAP and ARF Domains of ARF Domain Protein 1. Mol. Cell. Biol. 20: 7342-7352 [Abstract] [Full Text]
Sparrow, J. R., Nakanishi, K., Parish, C. A. (2000). The Lipofuscin Fluorophore A2E Mediates Blue Light-Induced Damage to Retinal Pigmented Epithelial Cells. IOVS 41: 1981-1989 [Abstract] [Full Text]
Sparrow, J. R., Parish, C. A., Hashimoto, M., Nakanishi, K. (1999). A2E, a Lipofuscin Fluorophore, in Human Retinal Pigmented Epithelial Cells in Culture. IOVS 40: 2988-2995 [Abstract] [Full Text]
Rodriguez, A., Martinez, I., Chung, A., Berlot, C. H., Andrews, N. W. (1999). cAMP Regulates Ca2+-dependent Exocytosis of Lysosomes and Lysosome-mediated Cell Invasion by Trypanosomes. J. Biol. Chem. 274: 16754-16759 [Abstract] [Full Text]
Vaughan, K., Tynan, S., Faulkner, N., Echeverri, C., Vallee, R. (1999). Colocalization of cytoplasmic dynein with dynactin and CLIP-170 at microtubule distal ends. J. Cell Sci. 112: 1437-1447 [Abstract]
Tuma, M. C., Zill, A., Le Bot, N., Vernos, I., Gelfand, V. (1998). Heterotrimeric Kinesin II Is the Microtubule Motor Protein Responsible for Pigment Dispersion in Xenopus Melanophores. JCB 143: 1547-1558 [Abstract] [Full Text]
Verhey, K. J., Lizotte, D. L., Abramson, T., Barenboim, L., Schnapp, B. J., Rapoport, T. A. (1998). Light Chain- dependent Regulation of Kinesin's Interaction with Microtubules. JCB 143: 1053-1066 [Abstract] [Full Text]
Vitale, N., Horiba, K., Ferrans, V. J., Moss, J., Vaughan, M. (1998). Localization of ADP-ribosylation factor domain protein 1�(ARD1) in lysosomes and Golgi apparatus. Proc. Natl. Acad. Sci. USA 95: 8613-8618 [Abstract] [Full Text]
Steinberg, G, Schliwa, M, Lehmler, C, Bolker, M, Kahmann, R, McIntosh, J. (1998). Kinesin from the plant pathogenic fungus Ustilago maydis is involved in vacuole formation and cytoplasmic migration. J. Cell Sci. 111: 2235-2246 [Abstract]
Daro, E., Sheff, D., Gomez, M., Kreis, T., Mellman, I. (1997). Inhibition of Endosome Function in CHO Cells Bearing a Temperature-sensitive Defect in the Coatomer (COPI) Component {varepsilon}-COP. JCB 139: 1747-1759 [Abstract] [Full Text]
Ward, D. M., Leslie, J. D., Kaplan, J. (1997). Homotypic Lysosome Fusion in Macrophages: Analysis Using an In Vitro Assay. JCB 139: 665-673 [Abstract] [Full Text]
Burkhardt, J. K., Echeverri, C. J., Nilsson, T., Vallee, R. B. (1997). Overexpression of the Dynamitin (p50) Subunit of the Dynactin Complex Disrupts Dynein-dependent Maintenance of Membrane Organelle Distribution. JCB 139: 469-484 [Abstract] [Full Text]
Nabi, I. R., Guay, G., Simard, D. (1997). AMF-R Tubules Concentrate in a Pericentriolar Microtubule Domain After MSV Transformation of Epithelial MDCK Cells. J. Histochem. Cytochem. 45: 1351-1364 [Abstract] [Full Text]
Agarraberes, F. A., Terlecky, S. R., Dice, J. F. (1997). An Intralysosomal hsp70 Is Required for a Selective Pathway of Lysosomal Protein Degradation. JCB 137: 825-834 [Abstract] [Full Text]
Blocker, A., Severin, F. F., Burkhardt, J. K., Bingham, J. B., Yu, H., Olivo, J.-C., Schroer, T. A., Hyman, A. A., Griffiths, G. (1997). Molecular Requirements for Bi-directional Movement of Phagosomes Along Microtubules. JCB 137: 113-129 [Abstract] [Full Text]
Nordstrom, T., Shrode, L. D., Rotstein, O. D., Romanek, R., Goto, T., Heersche, J. N.M., Manolson, M. F., Brisseau, G. F., Grinstein, S. (1997). Chronic Extracellular Acidosis Induces Plasmalemmal Vacuolar Type H+ ATPase Activity in Osteoclasts. J. Biol. Chem. 272: 6354-6360 [Abstract] [Full Text]
Burleigh, B. A., Caler, E. V., Webster, P., Andrews, N. W. (1997). A Cytosolic Serine Endopeptidase from Trypanosoma cruzi Is Required for the Generation of Ca2+ Signaling in Mammalian Cells. JCB 136: 609-620 [Abstract] [Full Text]
Wang, H., Benlimame, N, Nabi, I (1997). The AMF-R tubule is a smooth ilimaquinone-sensitive subdomain of the endoplasmic reticulum. J. Cell Sci. 110: 3043-3053 [Abstract]
Rajas, F., Gire, V., Rousset, B. (1996). Involvement of a Membrane-bound Form of Glutamate Dehydrogenase in the Association of Lysosomes to Microtubules. J. Biol. Chem. 271: 29882-29890 [Abstract] [Full Text]
Blocker, A., Severin, F. F., Habermann, A., Hyman, A. A., Griffiths, G., Burkhardt, J. K. (1996). Microtubule-associated Protein-dependent Binding of Phagosomes to Microtubules. J. Biol. Chem. 271: 3803-3811 [Abstract] [Full Text]
van Deurs, B, von Bulow, F, Vilhardt, F, Holm, P., Sandvig, K (1996). Destabilization of plasma membrane structure by prevention of actin polymerization. Microtubule-dependent tubulation of the plasma membrane. J. Cell Sci. 109: 1655-1665 [Abstract]
Burleigh, B. A., Andrews, N. W. (1995). A 120-kDa Alkaline Peptidase from Trypanosoma cruzi Is Involved in the Generation of a Novel Ca[IMAGE]-signaling Factor for Mammalian Cells. J. Biol. Chem. 270: 5172-5180 [Abstract] [Full Text]
Brickman, M., Cook, J., Balber, A. (1995). Low temperature reversibly inhibits transport from tubular endosomes to a perinuclear, acidic compartment in African trypanosomes. J. Cell Sci. 108: 3611-3621 [Abstract]
Sloane, B., Moin, K, Sameni, M, Tait, L., Rozhin, J, Ziegler, G (1994). Membrane association of cathepsin B can be induced by transfection of human breast epithelial cells with c-Ha-ras oncogene. J. Cell Sci. 107: 373-384 [Abstract]
Hamm-Alvarez, S., Kim, P., Sheetz, M. (1993). Regulation of vesicle transport in CV-1 cells and extracts. J. Cell Sci. 106: 955-966 [Abstract]
Perou, C., Kaplan, J (1993). Chediak-Higashi syndrome is not due to a defect in microtubule-based lysosomal mobility. J. Cell Sci. 106: 99-107 [Abstract]
Lin, S., Collins, C. (1993). Regulation of the intracellular distribution of cytoplasmic dynein by serum factors and calcium. J. Cell Sci. 105: 579-588 [Abstract]
Henson, J. H., Nesbitt, D., Wright, B. D., Scholey, J. M. (1992). Immunolocalization of kinesin in sea urchin coelomocytes. Association of kinesin with intracellular organelles. J. Cell Sci. 103: 309-320 [Abstract]
Parton, R. G., Schrotz, P., Bucci, C., Gruenberg, J. (1992). Plasticity of early endosomes. J. Cell Sci. 103: 335-348 [Abstract]
Bogner, P., Skehan, P., Kenney, S., Sainz, E., Akeson, M. A., Friedman, S. J. (1992). Stabilization of intercellular contacts in MDCK cells during Ca2+ deprivation. Selective effects of monocarboxylic acids on desmosomes. J. Cell Sci. 103: 463-473 [Abstract]
Guilherme, A., Emoto, M., Buxton, J. M., Bose, S., Sabini, R., Theurkauf, W. E., Leszyk, J., Czech, M. P. (2000). Perinuclear Localization and Insulin Responsiveness of GLUT4 Requires Cytoskeletal Integrity in 3T3-L1 Adipocytes. J. Biol. Chem. 275: 38151-38159 [Abstract] [Full Text]
Ong, L.-L., Lim, A. P. C., Er, C. P. N., Kuznetsov, S. A., Yu, H. (2000). Kinectin-Kinesin Binding Domains and Their Effects on Organelle Motility. J. Biol. Chem. 275: 32854-32860 [Abstract] [Full Text]
Dutoya, S., Gibert, S., Lemercier, G., Santarelli, X., Baltz, D., Baltz, T., Bakalara, N. (2001). A Novel C-terminal Kinesin Is Essential for Maintaining Functional Acidocalcisomes in Trypanosoma brucei. J. Biol. Chem. 276: 49117-49124 [Abstract] [Full Text]