1.A.87 The Mechanosensitive Calcium Channel (MCA) Family

Mechano-sensitive channels of plants sense increases in tension induced by mechanical stimuli, such as touch, wind, turgor pressure and gravitation. Plant homologues of MscS bacterial mechano-sensitive channels are known which are gated by membrane tension. Two of them have been shown to be involved in the protection of osmotically stressed plastids in Arabidopsis thaliana (see TC# 1.A.23.4.4). Membrane tension is not a mediator of long-range intracellular signaling, but local variations in tension mediate distinct processes in sub-cellular domains (Shi et al. 2018).

Iida et al. (2013) identified another group of candidates for mechano-sensitive channels in Arabidopsis, named MCA1 and MCA2, whose homologues are exclusively found in plant genomes. MCA1 and MCA2 are composed of 421 and 416 amino acyl residues, respectively, share 73% identity in their amino acid sequences, and are not homologous to any other known ion channels or transporters. A structural study revealed that the N-terminal region (~173 amino acids) of both proteins is necessary and sufficient for Ca2+ influx activity. This region has one putative transmembrane segment containing an Asp residue whose substitution mutation abolished activity.Their physiological study suggested that MCA1, expressed at the root tip, is required for sensing the hardness of the agar medium or soil. In addition, MCA1 and MCA2 were shown to be responsible for hypo-osmotic shock-induced increases in [Ca2+]cyt . Thus, both proteins appear to be involved in the process of sensing mechanical stresses. Iida et al. (2013) discussed the possible roles of both proteins in sensing mechanical and gravitational stimuli.  Several homologues may serve as receptors and regulatory proteins rather than ion channels, and several of these are included in this family in TCDB.  Their roles as mechanosensitive plasma membrane Ca2+-permeable channels, such as OsMCA1and OsMCA2 in rice seems to allow them to play roles in the generation of reactive oxygen species and in hypo-osmotic signaling (Kurusu et al. 2012; Kurusu et al. 2012; Kurusu et al. 2012).

MCA proteins show various topologies.  Several show a 1 + 3 TMS topology (subfamily 1) while others (subfamily 2) appear to have a 1 + 3 + 3 TMS topology, and still others have just 3 TMSs (subfamily 3).  The 3 TMSs in these last mentioned proteins appear to correspond to the last 3 TMSs in subfamilies 1 and 2. The topologies of subfamilies 4 and 5 are not clear.  There may be additional topological variations.

The generalized reaction reported to be catalyzed by MCA1 and MCA2 is:

Ca2+(out)  →  Ca2+ (in)



This family belongs to the Leucine-rich Repeat-containing Domain (LRRD) Superfamily.

 

References:

Choi, J., K. Tanaka, Y. Cao, Y. Qi, J. Qiu, Y. Liang, S.Y. Lee, and G. Stacey. (2014). Identification of a plant receptor for extracellular ATP. Science 343: 290-294.

Deng, C., B. Pan, M. Engel, and X.F. Huang. (2013). Neuregulin-1 signalling and antipsychotic treatment: potential therapeutic targets in a schizophrenia candidate signalling pathway. Psychopharmacology (Berl) 226: 201-215.

Hamilton, E.S., A.M. Schlegel, and E.S. Haswell. (2015). United in diversity: mechanosensitive ion channels in plants. Annu Rev Plant Biol 66: 113-137.

Iida H., Furuichi T., Nakano M., Toyota M., Sokabe M. and Tatsumi H. (2014). New candidates for mechano-sensitive channels potentially involved in gravity sensing in Arabidopsis thaliana. Plant Biol (Stuttg). 16 Suppl 1:39-42.

Kamano S., Kume S., Iida K., Lei KJ., Nakano M., Nakayama Y. and Iida H. (2015). Transmembrane Topologies of Ca2+-permeable Mechanosensitive Channels MCA1 and MCA2 in Arabidopsis thaliana. J Biol Chem. 290(52):30901-9.

Kurusu, T., D. Nishikawa, Y. Yamazaki, M. Gotoh, M. Nakano, H. Hamada, T. Yamanaka, K. Iida, Y. Nakagawa, H. Saji, K. Shinozaki, H. Iida, and K. Kuchitsu. (2012). Plasma membrane protein OsMCA1 is involved in regulation of hypo-osmotic shock-induced Ca2+ influx and modulates generation of reactive oxygen species in cultured rice cells. BMC Plant Biol 12: 11.

Kurusu, T., H. Iida, and K. Kuchitsu. (2012). Roles of a putative mechanosensitive plasma membrane Ca2+-permeable channel OsMCA1 in generation of reactive oxygen species and hypo-osmotic signaling in rice. Plant Signal Behav 7: 796-798.

Kurusu, T., T. Yamanaka, M. Nakano, A. Takiguchi, Y. Ogasawara, T. Hayashi, K. Iida, S. Hanamata, K. Shinozaki, H. Iida, and K. Kuchitsu. (2012). Involvement of the putative Ca²⁺-permeable mechanosensitive channels, NtMCA1 and NtMCA2, in Ca²⁺ uptake, Ca²⁺-dependent cell proliferation and mechanical stress-induced gene expression in tobacco (Nicotiana tabacum) BY-2 cells. J Plant Res 125: 555-568.

Lei, L. and A.C. Spradling. (2016). Mouse oocytes differentiate through organelle enrichment from sister cyst germ cells. Science 352: 95-99.

Libault, M. and G. Stacey. (2010). Evolution of FW2.2-like (FWL) and PLAC8 genes in eukaryotes. Plant Signal Behav 5: 1226-1228.

Oh, M.H., X. Wang, U. Kota, M.B. Goshe, S.D. Clouse, and S.C. Huber. (2009). Tyrosine phosphorylation of the BRI1 receptor kinase emerges as a component of brassinosteroid signaling in Arabidopsis. Proc. Natl. Acad. Sci. USA 106: 658-663.

Shi, Z., Z.T. Graber, T. Baumgart, H.A. Stone, and A.E. Cohen. (2018). Cell Membranes Resist Flow. Cell 175: 1769-1779.e13.

Shigematsu, H., K. Iida, M. Nakano, P. Chaudhuri, H. Iida, and K. Nagayama. (2014). Structural Characterization of the Mechanosensitive Channel Candidate MCA2 from Arabidopsis thaliana. PLoS One 9: e87724.

Song, W.Y., K.S. Choi, d.o.Y. Kim, M. Geisler, J. Park, V. Vincenzetti, M. Schellenberg, S.H. Kim, Y.P. Lim, E.W. Noh, Y. Lee, and E. Martinoia. (2010). Arabidopsis PCR2 is a zinc exporter involved in both zinc extrusion and long-distance zinc transport. Plant Cell 22: 2237-2252.

Song, W.Y., S. Hörtensteiner, R. Tomioka, Y. Lee, and E. Martinoia. (2011). Common functions or only phylogenetically related? The large family of PLAC8 motif-containing/PCR genes. Mol. Cells 31: 1-7.

Wang, C., J. Zhang, and J.I. Schroeder. (2017). Two-electrode Voltage-clamp Recordings in Xenopus laevis Oocytes: Reconstitution of Abscisic Acid Activation of SLAC1 Anion Channel via PYL9 ABA Receptor. Bio Protoc 7:.

Ward, N.L. and D.J. Dumont. (2002). The angiopoietins and Tie2/Tek: adding to the complexity of cardiovascular development. Semin Cell Dev Biol 13: 19-27.

Xiong, W., P. Wang, T. Yan, B. Cao, J. Xu, D. Liu, and M. Luo. (2018). The rice "fruit-weight 2.2-like" gene family member OsFWL4 is involved in the translocation of cadmium from roots to shoots. Planta. [Epub: Ahead of Print]

Examples:

TC#NameOrganismal TypeExample
1.A.87.1.1

Plant Ca2+ channel protein, Mid1 complementary activity 1, MCA1 (Iida et al. 2013).  MCA1 and MCA2 each forms a homotetramer and exhibit Ca2+-permeable MS channel activity.  Both are single-pass type I transmembrane proteins with their N-termini located extracellularly and their C-termini located intracellularly. An EF hand-like motif, coiled-coil motif, and Plac8 motif may all be in the cytoplasm, suggesting that the activities of both channels can be regulated by intracellular Ca2+ and protein interactions (Kamano et al. 2015). However, hydropathy plots suggest that the Plac8 domain may be transmembrane with 3 TMSs.  mca1 but not mca2 mutants show defects in root entry into hard agar, whereas mca2 but not mca1 mutants are defective in Ca2+ uptake in A. thaliana roots (Hamilton et al. 2015).

Plants

MCA1 of Arabidopsis thaliana

 
1.A.87.1.2

Plant Ca2+ channel protein, Mid1 complementary activity 2, MCA2 (Iida et al. 2013).  Catalyzes mechanical stress-induced Ca2+ influx.  It is tetrameric with a small transmembrane domain and a large cytoplasmic domain (Shigematsu et al. 2014).  MCA1 and MCA2 both have their N-termini located extracellularly and their C-termini located intracellularly. An EF hand-like motif, coiled-coil motif, and Plac8 motif may all be in the cytoplasm, suggesting that the activities of both channels can be regulated by intracellular Ca2+ and protein interactions (Kamano et al. 2015). However hydropathy plots suggest that the Plac8 domain may be transmembrane with 3 TMSs.  mca1 but not mca2 mutants show defects in root entry into hard agar, whereas mca2 but not mca1 mutants are defective in Ca2+ uptake in A. thaliana roots (Hamilton et al. 2015).

Plants

MCA2 of Arabidopsis thaliana

 
1.A.87.1.3

MCA1 isoform X2 of 377 aas

MCA1 of Solanum pennellii (Lycopersicon pennellii)

 
1.A.87.1.4

PLAC8 family protein of 385 aas.

PLAC8 family protein of Theobroma cacao
 
1.A.87.1.5

Mid1 complementing activity 1 of 154 aa

MCA1 of Vigna radiata

 
Examples:

TC#NameOrganismal TypeExample
1.A.87.2.1

Receptor protein kinase of 567 aas.  The first 140 aas are homologous to the N-terminal domains of MCA1 and 2; residues 240 - 430 are homologous to ser/thr protein kinases of 9.A.15.1.1, 9.B.45.1.3 and 9.B.106.3.1.

Plants

Receptor protein kinase of Zea mays

 
1.A.87.2.2

Protein kinase domain protein of 522 aas.

Plants

PKD protein of Oryza sativa

 
1.A.87.2.3

Receptor for extracellular ATP which functions in plant growth, development and stress responses; lectin receptor kinase 1.9; DORN1.  Binds ATP with high affinity (46nM) and is required ofr ATP-induced calcium response, mitogen-activated protein kinase activation and normal gene expression (Choi et al. 2014).

Plants

DORN1 of Arabidopsis thaliana

 
1.A.87.2.4

GHR1 (GUARD CELL HYDROGEN PEROXIDE-RESISTANT 1) transmembrane receptor-like protein of 1053 aas and 1 - 3 TMSs.  Regulates the SLAC1 protein (2.A.16.5.1) (Wang et al. 2017). The C-terminus shows extensive sequence similarity with members of this family, but the N-terminus shows similarity with members of family 3.A.20 (Leucine repeat proteins).

GHR1 of Arabidopsis thaliana

 
1.A.87.2.5

Uncharacterized protein with an ATP binding domain of 629 aas and 2 TMSs.

Plants

UP of Arabidopsis thaliana

 
1.A.87.2.6

Protein BRASSINOSTEROID INSENSITIVE 1, BRI1, of 1196 aas and 2 or 3 TMSs. Receptor with kinase activity acting on both serine/threonine- and tyrosine-containing substrates. In response to brassinosteroid binding, it regulates a signaling cascade involved in plant development, including expression of light- and stress-regulated genes, promotion of cell elongation, normal leaf and chloroplast senescence, and flowering. It binds brassinolide, and less effectively, castasterone (Oh et al. 2009).

BRI1 of Arabidopsis thaliana

 
Examples:

TC#NameOrganismal TypeExample
1.A.87.3.1

Plant cadmium resistance, PCR, protein of 164 aas.  Shows homology to the C-terminal PLAC8 domain of MCA1 and 2.

Plants

Cadmium resistance protein of Solanum lycopersicum (Tomato) (Lycopersicon esculentum)

 
1.A.87.3.10

Fruit-weight 2.2 protein of 197 aas and 3 TMSs.  May be involved in Cd2+ resistance as well as  translocation of Cd2+ from roots to shoots (Xiong et al. 2018). May form homooligomeric structures in the membrane.

FWL protein of Medicago truncatula (Barrel medic) (Medicago tribuloides)

 
1.A.87.3.11

Fruit-weight 2.2 protein of 161 aas and 4 TMSs.  May be involved in Cd2+ resistance as well as  translocation of Cd2+ from roots to shoots (Xiong et al. 2018).  May form homooligomeric structures in the membrane.

FWL protein of Medicago truncatula (Barrel medic) (Medicago tribuloides)

 
1.A.87.3.2

Plant Cadmium Resistance (PCR) protein. This protein corresponds to the C-terminal PLAC8 domain of MCA1 (TC# 1.A.87.1.1) (Song et al., 2011).

Plants

PLAC8 family protein of Arabidopsis thaliana

 
1.A.87.3.3

Sea squirt membrane protein of 110 aas

Animals

Membrane protein of Ciona intestinalis

 
1.A.87.3.4

Uncharacterized protein of 161 aas

Plants

UP of Capsella rubella

 
1.A.87.3.5

Plant cadmium resistance 6 protein, CadR6, of 224 aas.

Plants

CadR6 of Arabidopsis thaliana

 
1.A.87.3.6

Uncharacterized protein of 186 aas

Plants

UP of Glycine max

 
1.A.87.3.7

Plant cadmium resistance 1 protein of 151 aas and 2 TMSs. PCR1.  Involved in glutathione-independent cadmium resistance. Reduces cadmium uptake rather than activating efflux, but is not closely coupled to calcium transport (Song et al. 2011).

Plants

PCR1 of Arabidopsis thaliana

 
1.A.87.3.8

Plant cadmium resistance 2 (PCR2) protein.  Zinc ion exporter (Song et al. 2010; Song et al. 2011).  Involved in glutathione-independent cadmium resistance. Reduces cadmium uptake rather than activating efflux, but is not closely coupled to calcium transport.

Plants

PCR2 of Arabidopsis thaliana

 
1.A.87.3.9

FW2.2-like (FWL) protein of 180 aas and 2 TMSs.  Involved in plant and fruit development, and possibly in calcium transport (Libault and Stacey 2010).

Plants

FWL of Persea americanan (Avocado)

 
Examples:

TC#NameOrganismal TypeExample
1.A.87.4.1

Ubiquitin protein ligase with the first 250 aas homologous to MCA2.

Plants

Ubiquitin ligase of Physcomitrella patens

 
1.A.87.4.2

U box containing protein 15

Plants

U box protein of Solanum lycopersicum (Tomato) (Lycopersicon esculentum)

 
Examples:

TC#NameOrganismal TypeExample
1.A.87.5.1

Protein kinase_Tyr of 657 aas with N-terminal domain similar to that of MCA1, with N-terminal TMS containing a conserved aspartyl residue.

Fungi

PKinase-Tyr of Phanerochaete carnosa