Cytoplasmic dynein-2: from molecules to human diseases

Vidyalakshmi RAJAGOPALAN, Jonathan P. D’AMICO, David E. WILKES

PDF(339 KB)
PDF(339 KB)
Front. Biol. ›› 2013, Vol. 8 ›› Issue (1) : 119-126. DOI: 10.1007/s11515-012-1242-y
REVIEW
REVIEW

Cytoplasmic dynein-2: from molecules to human diseases

Author information +
History +

Abstract

The dynein motor protein family is involved in a wide variety of functions in eukaryotic cells. The axonemal dynein class and cytoplasmic dynein-1 subclass have been well characterized. However, the cytoplasmic dynein-2 subclass of the family has only recently begun to be understood. We describe the entire dynein family but focus on cytoplasmic dynein-2. Dynein-2 consists of a heavy, an intermediate, a light intermediate, and a light chain. The complex appears to function primarily as the retrograde motor for intraflagellar transport. This process is important for the formation and maintenance of cilia and flagella. Additionally, dynein-2 has roles in the control of ciliary length and in non-ciliary functions. Mutations in the human dynein-2 heavy chain lead to cilia-related diseases.

Keywords

cilia / dynein / flagella / intraflagellar transport / microtubule

Cite this article

Download citation ▾
Vidyalakshmi RAJAGOPALAN, Jonathan P. D’AMICO, David E. WILKES. Cytoplasmic dynein-2: from molecules to human diseases. Front Biol, 2013, 8(1): 119‒126 https://doi.org/10.1007/s11515-012-1242-y

References

[1]
Adhiambo C, Forney J D, Asai D J, LeBowitz J H (2005). The two cytoplasmic dynein-2 isoforms in Leishmania mexicana perform separate functions. Mol Biochem Parasitol, 143(2): 216–225
CrossRef Pubmed Google scholar
[2]
Asai D J, Beckwith S M, Kandl K A, Keating H H, Tjandra H, Forney J D (1994). The dynein genes of Paramecium tetraurelia. Sequences adjacent to the catalytic P-loop identify cytoplasmic and axonemal heavy chain isoforms. J Cell Sci, 107(Pt 4): 839–847
Pubmed
[3]
Asai D J, Brokaw C J (1993). Dynein heavy chain isoforms and axonemal motility. Trends Cell Biol, 3(11): 398–402
CrossRef Pubmed Google scholar
[4]
Asai D J, Rajagopalan V, Wilkes D E (2009). Dynein-2 and ciliogenesis in Tetrahymena. Cell Motil Cytoskeleton, 66(8): 673–677
CrossRef Pubmed Google scholar
[5]
Bae Y K, Lyman-Gingerich J, Barr M M, Knobel K M (2008). Identification of genes involved in the ciliary trafficking of C. elegans PKD-2. Dev Dyn, 237(8): 2021–2029
CrossRef Pubmed Google scholar
[6]
Blacque O E, Cevik S, Kaplan O I (2008). Intraflagellar transport: from molecular characterisation to mechanism. Front Biosci, 13(13): 2633–2652
CrossRef Pubmed Google scholar
[7]
Brokaw C J (1994). Control of flagellar bending: a new agenda based on dynein diversity. Cell Motil Cytoskeleton, 28(3): 199–204
CrossRef Pubmed Google scholar
[8]
Brokaw C J, Kamiya R (1987). Bending patterns of Chlamydomonas flagella: IV. Mutants with defects in inner and outer dynein arms indicate differences in dynein arm function. Cell Motil Cytoskeleton, 8(1): 68–75
CrossRef Pubmed Google scholar
[9]
Bruno K S, Tinsley J H, Minke P F, Plamann M (1996). Genetic interactions among cytoplasmic dynein, dynactin, and nuclear distribution mutants of Neurospora crassa. Proc Natl Acad Sci U S A, 93(10): 4775–4780
CrossRef Pubmed Google scholar
[10]
Burgess S A, Walker M L, Sakakibara H, Knight P J, Oiwa K (2003). Dynein structure and power stroke. Nature, 421(6924): 715–718
CrossRef Pubmed Google scholar
[11]
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. J Cell Biol, 139(2): 469–484
CrossRef Pubmed Google scholar
[12]
Criswell P S, Ostrowski L E, Asai D J (1996). A novel cytoplasmic dynein heavy chain: expression of DHC1b in mammalian ciliated epithelial cells. J Cell Sci, 109(Pt 7): 1891–1898
Pubmed
[13]
Dagoneau N, Goulet M, Geneviève D, Sznajer Y, Martinovic J, Smithson S, Huber C, Baujat G, Flori E, Tecco L, Cavalcanti D, Delezoide A L, Serre V, Le Merrer M, Munnich A, Cormier-Daire V (2009). DYNC2H1 mutations cause asphyxiating thoracic dystrophy and short rib-polydactyly syndrome, type III. Am J Hum Genet, 84(5): 706–711
CrossRef Pubmed Google scholar
[14]
Dutcher S K (1995). Flagellar assembly in two hundred and fifty easy-to-follow steps. Trends Genet, 11(10): 398–404
CrossRef Pubmed Google scholar
[15]
Eberl D F, Hardy R W, Kernan M J (2000). Genetically similar transduction mechanisms for touch and hearing in Drosophila. J Neurosci, 20(16): 5981–5988
Pubmed
[16]
Echeverri C J, Paschal B M, Vaughan K T, Vallee R B (1996). Molecular characterization of the 50-kD subunit of dynactin reveals function for the complex in chromosome alignment and spindle organization during mitosis. J Cell Biol, 132(4): 617–633
CrossRef Pubmed Google scholar
[17]
Ferkol T W, Leigh M W (2012). Ciliopathies: the central role of cilia in a spectrum of pediatric disorders. J Pediatr, 160(3): 366–371
CrossRef Pubmed Google scholar
[18]
Fridolfsson H N, Starr D A (2010). Kinesin-1 and dynein at the nuclear envelope mediate the bidirectional migrations of nuclei. J Cell Biol, 191(1): 115–128
CrossRef Pubmed Google scholar
[19]
Gibbons B H, Asai D J, Tang W J, Hays T S, Gibbons I R (1994). Phylogeny and expression of axonemal and cytoplasmic dynein genes in sea urchins. Mol Biol Cell, 5(1): 57–70
Pubmed
[20]
Gibbons B H, Gibbons I R (1973). The effect of partial extraction of dynein arms on the movement of reactivated sea-urchin sperm. J Cell Sci, 13(2): 337–357
Pubmed
[21]
Gibbons B H, Gibbons I R (1976). Functional recombination of dynein 1 with demembranated sea urchin sperm partially extracted with KC1. Biochem Biophys Res Commun, 73(1): 1–6
CrossRef Pubmed Google scholar
[22]
Gibbons I R (1963). Studies on the protein components of cilia from Tetrahymena pyriformis. Proc Natl Acad Sci U S A, 50(5): 1002–1010
CrossRef Pubmed Google scholar
[23]
Gibbons I R, Rowe A J (1965). Dynein: A protein with adenosine triphosphatase activity from cilia. Science, 149(3682): 424–426
CrossRef Pubmed Google scholar
[24]
Grissom P M, Vaisberg E A, McIntosh J R (2002). Identification of a novel light intermediate chain (D2LIC) for mammalian cytoplasmic dynein 2. Mol Biol Cell, 13(3): 817–829
CrossRef Pubmed Google scholar
[25]
Gross S P, Welte M A, Block S M, Wieschaus E F (2000). Dynein-mediated cargo transport in vivo. A switch controls travel distance. J Cell Biol, 148(5): 945–956
CrossRef Pubmed Google scholar
[26]
Harada A, Takei Y, Kanai Y, Tanaka Y, Nonaka S, Hirokawa N (1998). Golgi vesiculation and lysosome dispersion in cells lacking cytoplasmic dynein. J Cell Biol, 141(1): 51–59
CrossRef Pubmed Google scholar
[27]
Hildebrandt F, Benzing T, Katsanis N (2011). Ciliopathies. N Engl J Med, 364(16): 1533–1543
Pubmed
[28]
Hirokawa N, Sato-Yoshitake R, Yoshida T, Kawashima T (1990). Brain dynein (MAP1C) localizes on both anterogradely and retrogradely transported membranous organelles in vivo. J Cell Biol, 111(3): 1027–1037
CrossRef Pubmed Google scholar
[29]
Hou Y, Pazour G J, Witman G B (2004). A dynein light intermediate chain, D1bLIC, is required for retrograde intraflagellar transport. Mol Biol Cell, 15(10): 4382–4394
CrossRef Pubmed Google scholar
[30]
Huangfu D, Anderson K V (2005). Cilia and Hedgehog responsiveness in the mouse. Proc Natl Acad Sci U S A, 102(32): 11325–11330
CrossRef Pubmed Google scholar
[31]
Ichikawa M, Watanabe Y, Murayama T, Toyoshima Y Y (2011). Recombinant human cytoplasmic dynein heavy chain 1 and 2: observation of dynein-2 motor activity in vitro. FEBS Lett, 585(15): 2419–2423
CrossRef Pubmed Google scholar
[32]
Itin C, Ulitzur N, Mühlbauer B, Pfeffer S R (1999). Mapmodulin, cytoplasmic dynein, and microtubules enhance the transport of mannose 6-phosphate receptors from endosomes to the trans-golgi network. Mol Biol Cell, 10(7): 2191–2197
Pubmed
[33]
Kim J, Kato M, Beachy P A (2009). Gli2 trafficking links Hedgehog-dependent activation of Smoothened in the primary cilium to transcriptional activation in the nucleus. Proc Natl Acad Sci U S A, 106(51): 21666–21671
CrossRef Pubmed Google scholar
[34]
King S J, Bonilla M, Rodgers M E, Schroer T A (2002). Subunit organization in cytoplasmic dynein subcomplexes. Protein Sci, 11(5): 1239–1250
Pubmed
[35]
Koonce M P, Samsó M (1996). Overexpression of cytoplasmic dynein’s globular head causes a collapse of the interphase microtubule network in Dictyostelium. Mol Biol Cell, 7(6): 935–948
Pubmed
[36]
Krock B L, Mills-Henry I, Perkins B D (2009). Retrograde intraflagellar transport by cytoplasmic dynein-2 is required for outer segment extension in vertebrate photoreceptors but not arrestin translocation. Invest Ophthalmol Vis Sci, 50(11): 5463–5471
CrossRef Pubmed Google scholar
[37]
Lee E, Sivan-Loukianova E, Eberl D F, Kernan M J (2008). An IFT-A protein is required to delimit functionally distinct zones in mechanosensory cilia. Curr Biol, 18(24): 1899–1906
CrossRef Pubmed Google scholar
[38]
Lee S W, Wisniewski J C, Dentler W L, Asai D J (1999). Gene knockouts reveal separate functions for two cytoplasmic dyneins in Tetrahymena thermophila. Mol Biol Cell, 10(3): 771–784
Pubmed
[39]
Ma S, Triviños-Lagos L, Gräf R, Chisholm R L (1999). Dynein intermediate chain mediated dynein-dynactin interaction is required for interphase microtubule organization and centrosome replication and separation in Dictyostelium. J Cell Biol, 147(6): 1261–1274
CrossRef Pubmed Google scholar
[40]
Merrill A E, Merriman B, Farrington-Rock C, Camacho N, Sebald E T, Funari V A, Schibler M J, Firestein M H, Cohn Z A, Priore M A, Thompson A K, Rimoin D L, Nelson S F, Cohn D H, Krakow D (2009). Ciliary abnormalities due to defects in the retrograde transport protein DYNC2H1 in short-rib polydactyly syndrome. Am J Hum Genet, 84(4): 542–549
CrossRef Pubmed Google scholar
[41]
Mikami A, Tynan S H, Hama T, Luby-Phelps K, Saito T, Crandall J E, Besharse J C, Vallee R B (2002). Molecular structure of cytoplasmic dynein 2 and its distribution in neuronal and ciliated cells. J Cell Sci, 115(Pt 24): 4801–4808
CrossRef Pubmed Google scholar
[42]
Nishiura M, Kon T, Shiroguchi K, Ohkura R, Shima T, Toyoshima Y Y, Sutoh K (2004). A single-headed recombinant fragment of Dictyostelium cytoplasmic dynein can drive the robust sliding of microtubules. J Biol Chem, 279(22): 22799–22802
CrossRef Pubmed Google scholar
[43]
Ocbina P J, Anderson K V (2008). Intraflagellar transport, cilia, and mammalian Hedgehog signaling: analysis in mouse embryonic fibroblasts. Dev Dyn, 237(8): 2030–2038
CrossRef Pubmed Google scholar
[44]
Ocbina P J, Eggenschwiler J T, Moskowitz I, Anderson K V (2011). Complex interactions between genes controlling trafficking in primary cilia. Nat Genet, 43(6): 547–553
CrossRef Pubmed Google scholar
[45]
Palmer K J, Hughes H, Stephens D J (2009). Specificity of cytoplasmic dynein subunits in discrete membrane-trafficking steps. Mol Biol Cell, 20(12): 2885–2899
CrossRef Pubmed Google scholar
[46]
Palmer K J, MacCarthy-Morrogh L, Smyllie N, Stephens D J (2011). A role for Tctex-1 (DYNLT1) in controlling primary cilium length. Eur J Cell Biol, 90(10): 865–871
CrossRef Pubmed Google scholar
[47]
Paschal B M, Shpetner H S, Vallee R B (1987). MAP 1C is a microtubule-activated ATPase which translocates microtubules in vitro and has dynein-like properties. J Cell Biol, 105(3): 1273–1282
CrossRef Pubmed Google scholar
[48]
Pazour G J, Dickert B L, Witman G B (1999). The DHC1b (DHC2) isoform of cytoplasmic dynein is required for flagellar assembly. J Cell Biol, 144(3): 473–481
CrossRef Pubmed Google scholar
[49]
Pazour G J, Wilkerson C G, Witman G B (1998). A dynein light chain is essential for the retrograde particle movement of intraflagellar transport (IFT). J Cell Biol, 141(4): 979–992
CrossRef Pubmed Google scholar
[50]
Perrone C A, Tritschler D, Taulman P, Bower R, Yoder B K, Porter M E (2003). A novel dynein light intermediate chain colocalizes with the retrograde motor for intraflagellar transport at sites of axoneme assembly in Chlamydomonas and Mammalian cells. Mol Biol Cell, 14(5): 2041–2056
CrossRef Pubmed Google scholar
[51]
Pfister K K, Shah P R, Hummerich H, Russ A, Cotton J, Annuar A A, King S M, Fisher E M (2006). Genetic analysis of the cytoplasmic dynein subunit families. PLoS Genet, 2(1): e1
CrossRef Pubmed Google scholar
[52]
Porter M E (1996). Axonemal dyneins: assembly, organization, and regulation. Curr Opin Cell Biol, 8(1): 10–17
CrossRef Pubmed Google scholar
[53]
Porter M E, Bower R, Knott J A, Byrd P, Dentler W (1999). Cytoplasmic dynein heavy chain 1b is required for flagellar assembly in Chlamydomonas. Mol Biol Cell, 10(3): 693–712
Pubmed
[54]
Rajagopalan V, Subramanian A, Wilkes D E, Pennock D G, Asai D J (2009). Dynein-2 affects the regulation of ciliary length but is not required for ciliogenesis in Tetrahymena thermophila. Mol Biol Cell, 20(2): 708–720
CrossRef Pubmed Google scholar
[55]
Rana A A, Barbera J P, Rodriguez T A, Lynch D, Hirst E, Smith J C, Beddington R S (2004). Targeted deletion of the novel cytoplasmic dynein mD2LIC disrupts the embryonic organiser, formation of the body axes and specification of ventral cell fates. Development, 131(20): 4999–5007
CrossRef Pubmed Google scholar
[56]
Reck-Peterson S L, Yildiz A, Carter A P, Gennerich A, Zhang N, Vale R D (2006). Single-molecule analysis of dynein processivity and stepping behavior. Cell, 126(2): 335–348
CrossRef Pubmed Google scholar
[57]
Rompolas P, Pedersen L B, Patel-King R S, King S M (2007). Chlamydomonas FAP133 is a dynein intermediate chain associated with the retrograde intraflagellar transport motor. J Cell Sci, 120(Pt 20): 3653–3665
CrossRef Pubmed Google scholar
[58]
Rosenbaum J L, Witman G B (2002). Intraflagellar transport. Nat Rev Mol Cell Biol, 3(11): 813–825
CrossRef Pubmed Google scholar
[59]
Sakato M, King S M (2004). Design and regulation of the AAA+ microtubule motor dynein. J Struct Biol, 146(1-2): 58–71
CrossRef Pubmed Google scholar
[60]
Salina D, Bodoor K, Eckley D M, Schroer T A, Rattner J B, Burke B (2002). Cytoplasmic dynein as a facilitator of nuclear envelope breakdown. Cell, 108(1): 97–107
CrossRef Pubmed Google scholar
[61]
Schafer J C, Haycraft C J, Thomas J H, Yoder B K, Swoboda P (2003). XBX-1 encodes a dynein light intermediate chain required for retrograde intraflagellar transport and cilia assembly in Caenorhabditis elegans. Mol Biol Cell, 14(5): 2057–2070
CrossRef Pubmed Google scholar
[62]
Schnapp B J, Reese T S (1989). Dynein is the motor for retrograde axonal transport of organelles. Proc Natl Acad Sci U S A, 86(5): 1548–1552
CrossRef Pubmed Google scholar
[63]
Scholey J M (2003). Intraflagellar transport. Annu Rev Cell Dev Biol, 19(1): 423–443
CrossRef Pubmed Google scholar
[64]
Signor D, Wedaman K P, Orozco J T, Dwyer N D, Bargmann C I, Rose L S, Scholey J M (1999). Role of a class DHC1b dynein in retrograde transport of IFT motors and IFT raft particles along cilia, but not dendrites, in chemosensory neurons of living Caenorhabditis elegans. J Cell Biol, 147(3): 519–530
CrossRef Pubmed Google scholar
[65]
Söhle J, Machuy N, Smailbegovic E, Holtzmann U, Grönniger E, Wenck H, Stäb F, Winnefeld M (2012). Identification of new genes involved in human adipogenesis and fat storage. PLoS One, 7(2): e31193
CrossRef Pubmed Google scholar
[66]
Thiel C, Kessler K, Giessl A, Dimmler A, Shalev S A, von der Haar S, Zenker M, Zahnleiter D, Stöss H, Beinder E, Abou Jamra R, Ekici A B, Schröder-Kress N, Aigner T, Kirchner T, Reis A, Brandstätter J H, Rauch A (2011). NEK1 mutations cause short-rib polydactyly syndrome type majewski. Am J Hum Genet, 88(1): 106–114
CrossRef Pubmed Google scholar
[67]
Vaisberg E A, Grissom P M, McIntosh J R (1996). Mammalian cells express three distinct dynein heavy chains that are localized to different cytoplasmic organelles. J Cell Biol, 133(4): 831–842
CrossRef Pubmed Google scholar
[68]
Vale R D (2003). The molecular motor toolbox for intracellular transport. Cell, 112(4): 467–480
CrossRef Pubmed Google scholar
[69]
Wicks S R, de Vries C J, van Luenen H G, Plasterk R H (2000). CHE-3, a cytosolic dynein heavy chain, is required for sensory cilia structure and function in Caenorhabditis elegans. Dev Biol, 221(2): 295–307
CrossRef Pubmed Google scholar
[70]
Wilkie G S, Davis I (2001). Drosophila wingless and pair-rule transcripts localize apically by dynein-mediated transport of RNA particles. Cell, 105(2): 209–219
CrossRef Pubmed Google scholar
[71]
Willemsen M H, Vissers L E, Willemsen M A, van Bon B W, Kroes T, de Ligt J, de Vries B B, Schoots J, Lugtenberg D, Hamel B C, van Bokhoven H, Brunner H G, Veltman J A, Kleefstra T (2012). Mutations in DYNC1H1 cause severe intellectual disability with neuronal migration defects. J Med Genet, 49(3): 179–183
CrossRef Pubmed Google scholar
[72]
Woźniak M J, Bola B, Brownhill K, Yang Y C, Levakova V, Allan V J (2009). Role of kinesin-1 and cytoplasmic dynein in endoplasmic reticulum movement in VERO cells. J Cell Sci, 122(Pt 12): 1979–1989
CrossRef Pubmed Google scholar
[73]
Xiang X, Beckwith S M, Morris N R (1994). Cytoplasmic dynein is involved in nuclear migration in Aspergillus nidulans. Proc Natl Acad Sci U S A, 91(6): 2100–2104
CrossRef Pubmed Google scholar
[74]
Zheng Y, Wildonger J, Ye B, Zhang Y, Kita A, Younger S H, Zimmerman S, Jan L Y, Jan Y N (2008). Dynein is required for polarized dendritic transport and uniform microtubule orientation in axons. Nat Cell Biol, 10(10): 1172–1180
CrossRef Pubmed Google scholar

Acknowledgments

We thank all the past and present members of the Asai and Wilkes laboratories who have contributed to our knowledge of cytoplasmic dynein-2 in Tetrahymena, Paramecium, and rat. Our laboratory is supported by a grant from the National Science Foundation.

RIGHTS & PERMISSIONS

2014 Higher Education Press and Springer-Verlag Berlin Heidelberg
PDF(339 KB)

Accesses

Citations

Detail

Sections
Recommended

/