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Plant Signal Behav. 2012 March 1; 7(3): 345–348.
PMCID: PMC3443916

Cadmium toxicity

Effects on cytoskeleton, vesicular trafficking and cell wall construction


Cadmium is a well-known environmental pollutant with distinctly toxic effects on plants. It can displace certain essential metals from a wealth of metalloproteins, and thus disturb many normal physiological processes and cause severe developmental aberrant. The harmful effects of cadmium stress include, but are not limited to: reactive oxygen species overproduction, higher lipid hydroperoxide contents, and chloroplast structure change, which may lead to cell death. Plants have developed diverse mechanisms to alleviate environmental cadmium stress, e.g., cadmium pump and transporting cadmium into the leaf vacuoles. This mini-review focuses on the current research into understanding the cellular mechanisms of cadmium toxicity on cytoskeleton, vesicular trafficking and cell wall formation in plants.

Keywords: actin cytoskeleton, cadmium, cell wall construction, vesicular trafficking


Cadmium (Cd) contamination causes serious environmental problems for modern agriculture and human health.1 Cadmium is one of the most toxic and non-essential heavy metals.2 However, the mechanisms underlying the toxic effects are still largely unknown. Due to its chemical similarity to certain essential mineral elements, e.g., Zn, Fe and Ca, cadmium toxicity rises from displacement of these essential elements from a number of essential metalloproteins.3 It was mainly present as a protein-bound form in plants. The displacement of certain divalent cations such as Zn and Fe from metalloproteins gives rise to the release of “free” ions that can lead to oxidative injury via free Fe/Cu-catalyzed Fenton reactions.4 Moreover, because of its high affinity for sulphydrl groups of proteins or enzymes, it inactivates many SH-bearing, redox-regulated enzymes in many cellular processes.5 Cadmium can be accumulated in leaves and cause phytotoxic effect on plants, such as chloroplast structure change, reactive oxygen species (ROS) production and cell death.6 ROS production via NADPH oxidases seems important in oxidative stress caused by cadmium in Arabidopsis thaliana.7 Lipid hydroperoxide contents are higher after cadmium-treatment, producing lysophosphatidylcholine which damages the phospholipid.8

Cadmium and Cytoskeleton

Cytoskeleton plays an important role in several cellular functions, including apoptosis and cell survival.9 Cadmium toxicity to cytoskeleton was well studied in animal cells. Kunimoto et al. (1986) reported a time-dependent positive correlation, in intact cells, between the amount of cadmium bound to the cytoskeleton and the amount of integral membrane protein that could be isolated with the cytoskeleton, indicating that cadmium may act directly on the cytoskeleton.10 Exposure to cadmium leads to disassembly of microtubules in intact Swiss 3T3 cells.11 In mouse mesangial cells (MMC), 10 μmol/L cadmium caused actin filament disruption and loss of stress fibers by 4 h. Actin staining became irregular in most cells and was lost completely in some cells by 6 h.12

However effect of cadmium on the arrangement of cytoskeleton in plant cells was less reported. Přibyl et al. (2005) revealed the toxic effect of cadmium on the cytoskeleton in interphase cells of the green alga Spirogyra decimina. They found that microtubules were more sensitive to cadmium exposure than actin filaments. Microtubules reoriented or aggregated into short rod-shaped fragments and then completely disappeared in a dose- and time-dependent manner after cadmium treatment. Actin filaments were disintegrated several hours later than microtubules.13 Fusconi et al. (2007)14 compared microtubular arrangement with other parameters usually used in environmental monitoring, such as root length, mitotic index and occurrence of mitotic aberrations, in cadmium-exposed root apical meristems of Pisum sativum L. The microtubule cytoskeleton appeared to be highly sensitive to the presence of cadmium and can be used as a marker for assessment of cadmium pollution.14 Recently, the effect of cadmium on arrangement of actin filaments was studied in Arabidopsis.15 Actin filaments were markedly disrupted depending on the cadmium concentration and the time of treatment in root hairs. Treatment with 5 μM cadmium destroyed the arrangement of actin filaments, changing them from a longitudinal to a transverse array. With increasing cadmium concentrations, longitudinal AFs completely disappeared, indicating that cytoskeletal disarrangement is an important component of metal ion toxicity. Besides direct interaction of cadmium with cytoskeleton as observed in animal cells, another possible mechanism by which cadmium exposure could lead to an alteration in the pattern of actin cytoskeleton is via an effect on calcium metabolism and transport.16,17 Many cytoskeletal proteins, including some actin-associated proteins, are sensitive to changes in calcium. It was reported that increase of calcium concentration results in destabilization and depolymerization of actin.18 However, Fan et al. found that the cytoplasmic concentration of calcium decreased in cadmium-treated Arabidopsis root hairs.15 Therefore it is possible that that cadmium might mimic calcium to activate actin filament-severing proteins and thus lead to actin filaments depolymerization. Calcium in the crystal structure of gelsolin, a calcium-dependent actin-severing protein, can be reportedly replaced by cadmium, indicating that cadmium can activate gelsolin for actin filament binding and severing.19 Apostolova et al. also demonstrated that cadmium activates the association of gelsolin with actin cytoskeleton, with gelsolin’s severing properties.20

Cadmium and Vesicular Trafficking

Intracellular transport is critical for the delivery of membrane-bounded vesicles and organelles to various cellular destinations and for the spatial organization of endomembranes.21 Vesicular trafficking occurs along the endocytic (import) or secretory/exocytosis (export) pathways. The driving force for vesicular transport is provided by vesicle-bound molecular motors, which interact with cytoskeletal elements, microtubules or actin filaments. These elements can serve as “tracks” for the vesicle transport. In animal cells, microtubules generally act as tracks for transport over long distances, whereas actin filaments support the local movement of vesicles.22,23 In plant cells, however, vesicles are transported along actin fibers by myosin motor molecules.24-27 Fan et al. labeled the endocytic vesicles using the fluorescent membrane dye FM4-64 to observe whether cadmium treatment influenced endocytosis and vesicular transport in root hair cells.15 Their time-lapse images of cadmium-treated root hairs showed that the FM dye staining pattern was obviously distinct from that of control cells, suggesting that membrane endocytosis and vesicular trafficking were perturbed during cadmium stress and this perturbation might result from the cadmium-induced-disruption of the “tracks” (actin filaments) for vesicle transport (Fig. 1).

Figure 1.
Hypothetical model showing summarizing main effects of CdCl2 treatment on the tip growth of Arabidopsis root hair. Cd entered the cell through a still unidentified metal transporter or Ca2+ channels by mimicking Ca2+ ions. Disruption of the structure ...

Exocytosis, the reverse of endocytosis, is a process by which the contents of secretory vesicles are transported into extracellular space. In yeast and humans, exocytosis via metal-containing vesicles had been documented as an important means of metal tolerance.28 Secretory pathway Ca/Mn-ATPases which are localized on Golgi or trans-Golgi network (TGN) serve a physiological role in the sequestration of manganese into secretory vesicles and subsequent release of manganese.29 Recently, yeast Ca-ATPase, Pmr1p, was also demonstrated to play a central role in the secretion of cadmium through the secretory pathway.30 Similar mechanism has now been reported in plants. Peiter et al. showed that MTP11, a member of CDF (cation diffusion facilitators) family in Arabidopsis, was localized on trans-Golgi vesicles and believed to confer manganese tolerance.31 Expression of MTP11 in rescued manganese sensitivity of pmr1Δ deletion yeast via microsomal loading. Loss of function mutation of MTP11 in Arabidopsis led to hypersensitivity to manganese, whereas overexpression of MTP11 in Arabidopsis enhanced manganese tolerance, suggesting that excess manganese was sequestered by MTP11 into vesicles and then exocytosed.

Cadmium and Cell Wall Construction

The plant cell wall is a dynamic structure that is mainly composed of cellulose microfibrils embedded in a matrix of hemicellulose and pectic polysaccharides.32 Cadmium has deep effects on the composition of cell wall.33-36 Huttová et al.37 analyzed changes in peroxidase activity as well as isozyme peroxidase pattern in five cell wall (CW) fractions of barley roots treated with 1 mM cadmium for 48 h and 72 h, whereas strong inhibition of peroxidase activity was observed in fraction CW I and weak inhibition in fractions CW II, III and IV, strong activation of peroxidase was detected in fraction V. Despite the inhibition of enzyme activity in most cell wall fractions, induction of several isoperoxidases was detected after separation on PAGE.37 Douchiche et al. found cadmium treatment induced an increase of the amount of cellulose.38 Moreover, negatively charged cellulose and cellulose derivatives was found to bind with cadmium in mycorrhizal fungi after cadmium treatment.39 Xiong et al. concluded that decreased distribution of cadmium in the soluble fraction of leaves and roots and increased distribution of cadmium in the cell walls of roots were responsible for the nitrogen monoxide-induced increase of cadmium tolerance in rice.40 Excessive lignin production induced by cadmium accounted for the solidification of cell wall and subsequent restriction of root growth.41 The distribution of de-esterified and esterified pectins on the radical apex differed with different concentrations of cadmium, indicating that cadmium spatially modulates the synthesis and distribution of both pectins.15 In addition, de-esterified pectins can bind with calcium by their carboxyl groups and thus increase stiffening of cell wall, which contribute to inhibition of cell expansion. Other polysaccharides and components in the cell wall such as cellulose, semi-cellulose and proteins also play a crucial role in metal binding and accumulation. FTIR analysis and immunolabeling results showed that cellulose was preferentially deposited in the apical dome of cadmium-treated roots, suggesting that constraint of cadmium by excess cellulose may partly account for detoxification of cadmium in the tip zone of root hairs.

Conclusions and Prospective

Recent researches have made significant progress on the understanding of the underlying molecular mechanisms of cadmium toxicity to plants. Excessive cadmium exposure can lead to reduced calcium concentration which causes disassembling of actin filaments. Consequently, variation of vesicular trafficking and disturbance of cell wall construction lead to inhibition of cell growth. It will be an important goal of future research to unravel the identity of cadmium-induced actin severing proteins and vesicular trafficking-related proteins to analyze their functional role in cadmium toxicity. The cell wall has been recognized as a compartment of active metabolism. Exposure to heavy metals (cadmium or nickel) leads to a significant de novo synthesis of proteins released into the extracellular space. Therefore, more work needs to be done to elucidate the function of the extracellular compartment in heavy metal signal transmission and detoxification.


This work was financially supported by the National Natural Science Foundation of China (NSFC) (No. 90817010 and 30770123), the National Basic Research Program of China (973) (No. 2007CB108904) and the National High Technology Research and Development Program of China (863) (No. 2008AA10Z130).



1. Liang HM, Lin TH, Chiou JM, Yeh KC. Model evaluation of the phytoextraction potential of heavy metal hyperaccumulators and non-hyperaccumulators. Environ Pollut. 2009;157:1945–52. [PubMed]
2. Tian S, Lu L, Labavitch J, Yang X, He Z, Hu H, et al. Cellular sequestration of cadmium in the hyperaccumulator plant species Sedum alfredii. Plant Physiol. 2011;157:1914–25. [PubMed]
3. Herbette S, Taconnat L, Hugouvieux V, Piette L, Magniette ML, Cuine S, et al. Genome-wide transcriptome profiling of the early cadmium response of Arabidopsis roots and shoots. Biochimie. 2006;88:1751–65. [PubMed]
4. Stohs SJ, Bagchi D, Hassoun E, Bagchi M. Oxidative mechanisms in the toxicity of chromium and cadmium ions. J Environ Pathol Toxicol Oncol. 2000;19:201–13. [PubMed]
5. Hall JL. Cellular mechanisms for heavy metal detoxification and tolerance. J Exp Bot. 2002;53:1–11. [PubMed]
6. Cuypers A, Smeets K, Ruytinx J, Opdenakker K, Keunen E, Remans T, et al. The cellular redox state as a modulator in cadmium and copper responses in Arabidopsis thaliana seedlings. J Plant Physiol. 2011;168:309–16. [PubMed]
7. Banakou E, Dailianis S. Involvement of Na+/H+ exchanger and respiratory burst enzymes NADPH oxidase and NO synthase, in Cd-induced lipid peroxidation and DNA damage in haemocytes of mussels. Comp Biochem Physiol C Toxicol Pharmacol. 2010;152:346–52. [PubMed]
8. Gao W, Li HY, Xiao S, Chye ML. Acyl-CoA-binding protein 2 binds lysophospholipase 2 and lysoPC to promote tolerance to cadmium-induced oxidative stress in transgenic Arabidopsis. Plant J. 2010;62:989–1003. [PubMed]
9. Papakonstanti EA, Stournaras C. Cell responses regulated by early reorganization of actin cytoskeleton. FEBS Lett. 2008;582:2120–7. [PubMed]
10. Kunimoto M, Miyasaka K, Miura T. Changes in membrane properties of rat red blood cells induced by cadmium accumulating in the membrane fraction. J Biochem. 1986;99:397–406. [PubMed]
11. Perrino BA, Chou IN. Role of calmodulin in cadmium-induced microtubule disassembly. Cell Biol Int Rep. 1986;10:565–73. [PubMed]
12. Liu Y, Templeton DM. Role of the cytoskeleton in Cd2+-induced death of mouse mesangial cells. Can J Physiol Pharmacol. 2010;88:341–52. [PubMed]
13. Přibyl P, Cepák V, Zachleder V. Cytoskeletal alterations in interphase cells of the green alga Spirogyra decimina in response to heavy metals exposure: I. The effect of cadmium. Protoplasma. 2005;226:231–40. [PubMed]
14. Fusconi A, Gallo C, Camusso W. Effects of cadmium on root apical meristems of Pisum sativum L.: cell viability, cell proliferation and microtubule pattern as suitable markers for assessment of stress pollution. Mutat Res. 2007;632:9–19. [PubMed]
15. Fan JL, Wei XZ, Wan LC, Zhang LY, Zhao XQ, Liu WZ, et al. Disarrangement of actin filaments and Ca²+ gradient by CdCl₂ alters cell wall construction in Arabidopsis thaliana root hairs by inhibiting vesicular trafficking. J Plant Physiol. 2011;168:1157–67. [PubMed]
16. Webb M. Functions of hepatic and renal metallothioneins in the control of the metabolism of cadmium and certain other bivalent cations. Experientia Suppl. 1979;34:313–20. [PubMed]
17. Verbost PM, Flik G, Lock RA, Wendelaar Bonga SE. Cadmium inhibits plasma membrane calcium transport. J Membr Biol. 1988;102:97–104. [PubMed]
18. Zhang H, Qu X, Bao C, Khurana P, Wang Q, Xie Y, et al. Arabidopsis VILLIN5, an actin filament bundling and severing protein, is necessary for normal pollen tube growth. Plant Cell. 2010;22:2749–67. [PubMed]
19. Kazmirski SL, Isaacson RL, An C, Buckle A, Johnson CM, Daggett V, et al. Loss of a metal-binding site in gelsolin leads to familial amyloidosis-Finnish type. Nat Struct Biol. 2002;9:112–6. [PubMed]
20. Apostolova MD, Christova T, Templeton DM. Involvement of gelsolin in cadmium-induced disruption of the mesangial cell cytoskeleton. Toxicol Sci. 2006;89:465–74. [PubMed]
21. Lane J, Allan V. Microtubule-based membrane movement. Biochim Biophys Acta. 1998;1376:27–55. [PubMed]
22. Langford GM. Actin- and microtubule-dependent organelle motors: interrelationships between the two motility systems. Curr Opin Cell Biol. 1995;7:82–8. [PubMed]
23. Ross JL, Ali MY, Warshaw DM. Cargo transport: molecular motors navigate a complex cytoskeleton. Curr Opin Cell Biol. 2008;20:41–7. [PMC free article] [PubMed]
24. Parton RM, Fischer-Parton S, Watahiki MK, Trewavas AJ. Dynamics of the apical vesicle accumulation and the rate of growth are related in individual pollen tubes. J Cell Sci. 2001;114:2685–95. [PubMed]
25. Wang X, Teng Y, Wang Q, Li X, Sheng X, Zheng M, et al. Imaging of dynamic secretory vesicles in living pollen tubes of Picea meyeri using evanescent wave microscopy. Plant Physiol. 2006;141:1591–603. [PubMed]
26. Justus CD, Anderhag P, Goins JL, Lazzaro MD. Microtubules and microfilaments coordinate to direct a fountain streaming pattern in elongating conifer pollen tube tips. Planta. 2004;219:103–9. [PubMed]
27. Voigt B, Timmers AC, Šamaj J, Hlavacka A, Ueda T, Preuss M, et al. Actin-based motility of endosomes is linked to the polar tip growth of root hairs. Eur J Cell Biol. 2005;84:609–21. [PubMed]
28. Morrissey J, Guerinot ML. Trace elements: too little or too much and how plants cope. F1000 Biol Rep. 2009;1:14. [PMC free article] [PubMed]
29. Xiang M, Mohamalawari D, Rao R. A novel isoform of the secretory pathway Ca2+,Mn(2+)-ATPase, hSPCA2, has unusual properties and is expressed in the brain. J Biol Chem. 2005;280:11608–14. [PubMed]
30. Lauer Júnior CM, Bonatto D, Mielniczki-Pereira AA, Schuch AZ, Dias JF, Yoneama ML, et al. The Pmr1 protein, the major yeast Ca2+-ATPase in the Golgi, regulates intracellular levels of the cadmium ion. FEMS Microbiol Lett. 2008;285:79–88. [PubMed]
31. Peiter E, Montanini B, Gobert A, Pedas P, Husted S, Maathuis FJ, et al. A secretory pathway-localized cation diffusion facilitator confers plant manganese tolerance. Proc Natl Acad Sci U S A. 2007;104:8532–7. [PubMed]
32. Popper ZA, Michel G, Hervé C, Domozych DS, Willats WG, Tuohy MG, et al. Evolution and diversity of plant cell walls: from algae to flowering plants. Annu Rev Plant Biol. 2011;62:567–90. [PubMed]
33. Kováčik J, Klejdus B, Hedbavny J, Zoń J. Significance of phenols in cadmium and nickel uptake. J Plant Physiol. 2011;168:576–84. [PubMed]
34. Fu X, Dou C, Chen Y, Chen X, Shi J, Yu M, et al. Subcellular distribution and chemical forms of cadmium in Phytolacca americana L. J Hazard Mater. 2011;186:103–7. [PubMed]
35. Kovácik J, Klejdus B, Stork F, Hedbavny J. Nitrate deficiency reduces cadmium and nickel accumulation in chamomile plants. J Agric Food Chem. 2011;59:5139–49. [PubMed]
36. Piršelová B, Kuna R, Libantová J, Moravčíková J, Matušíková I. Biochemical and physiological comparison of heavy metal-triggered defense responses in the monocot maize and dicot soybean roots. Mol Biol Rep. 2011;38:3437–46. [PubMed]
37. Huttová J, Mistrík I, Ollé-Šimonovičová M, Tamás L. Cadmium induced changes in cell wall peroxidase isozyme pattern in barley root tips. Plant Soil Environ. 2006;52:250–3.
38. Douchiche O, Rihouey C, Schaumann A, Driouich A, Morvan C. Cadmium-induced alterations of the structural features of pectins in flax hypocotyl. Planta. 2007;225:1301–12. [PubMed]
39. González-Guerrero M, Melville LH, Ferrol N, Lott JN, Azcón-Aguilar C, Peterson RL. Ultrastructural localization of heavy metals in the extraradical mycelium and spores of the arbuscular mycorrhizal fungus Glomus intraradices. Can J Microbiol. 2008;54:103–10. [PubMed]
40. Xiong J, An L, Lu H, Zhu C. Exogenous nitric oxide enhances cadmium tolerance of rice by increasing pectin and hemicellulose contents in root cell wall. Planta. 2009;230:755–65. [PubMed]
41. Finger-Teixeira A, Ferrarese MdeL, Soares AR, da Silva D, Ferrarese-Filho O. Cadmium-induced lignification restricts soybean root growth. Ecotoxicol Environ Saf. 2010;73:1959–64. [PubMed]

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