LmxMPK9, a mitogen‐activated protein kinase homologue affects flagellar length in <i> Leishmania mexicana</i>

Bengs, Florian; Scholz, Anne; Kuhn, Daniela; Wiese, Martin

doi:10.1111/j.1365-2958.2005.04498.x

Cited by 121 publications

(116 citation statements)

References 34 publications

(45 reference statements)

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“…DYF-5 encodes a putative MAP kinase that regulates the length of sensory cilia in C. elegans, similar to what has been reported for DYF-5 homologues in Chlamydomonas (LF4) and Leishmania (LmxMPK9) (17,18): dyf-5 loss-of-function results in cilia elongation, whereas overexpression results in shorter cilia. In addition, fluorescence and EM showed that, in the absence of DYF-5, the cilia are more dispersed and that many cilia are not properly aligned into the amphid channel and sometimes turn back to the base, although some cilia do enter the channel.…”

Section: Discussionmentioning

confidence: 72%

“…We wondered whether mutations in dyf-5 affect cilia morphology and length, as in Chlamydomonas and Leishmania (17,18). Visualization of the microtubular axonemes of the cilia using anti-tubulin antibodies revealed that the cilia of dyf-5(lf) animals were not properly aligned into the amphid pore.…”

Section: Mutation Of Dyf-5 Affects Cilia Morphology and Lengthmentioning

confidence: 99%

“…Although the functions of these kinases in mammals are not known, studies in other organisms suggest a function in the cilia. Mutations in a DYF-5 homologue in Leishmania mexicana, LmxMPK9 (17), and in one of the two homologues in Chlamydomonas reinhardtii, LF4 (18), affect the length of the flagella of these organisms. In addition, several genome-wide approaches have identified DYF-5 and its homologues as likely ciliary proteins (21,(26)(27)(28)(29)(30).…”

mentioning

confidence: 99%

“…Not much is known about the molecular mechanisms that control length and morphology of cilia, although it has been proposed that cilia length is controlled by a balance between cilia assembly and disassembly regulated by IFT (12)(13)(14). Genetic approaches have thus far identified three proteins involved in the regulation of cilia length: two Chlamydomonas reinhardtii proteins, LF1 and LF2, and the Chlamydomonas MAP kinase LF4 and its Leishmania mexicana homologue LmxMPK9 (15)(16)(17)(18).…”

mentioning

confidence: 99%

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Mutation of the MAP kinase DYF-5 affects docking and undocking of kinesin-2 motors and reduces their speed in the cilia of Caenorhabditis elegans

Burghoorn¹,

Dekkers²,

Rademakers³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

111

181

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In the cilia of the nematode Caenorhabditis elegans, anterograde intraflagellar transport (IFT) is mediated by two kinesin-2 complexes, kinesin II and OSM-3 kinesin. These complexes function together in the cilia middle segments, whereas OSM-3 alone mediates transport in the distal segments. Not much is known about the mechanisms that compartmentalize the kinesin-2 complexes or how transport by both kinesins is coordinated. Here, we identify DYF-5, a conserved MAP kinase that plays a role in these processes. Fluorescence microscopy and EM revealed that the cilia of dyf-5 loss-of-function (lf) animals are elongated and are not properly aligned into the amphid channel. Some cilia do enter the amphid channel, but the distal ends of these cilia show accumulation of proteins. Consistent with these observations, we found that six IFT proteins accumulate in the cilia of dyf-5(lf) mutants. In addition, using genetic analyses and live imaging to measure the motility of IFT proteins, we show that dyf-5 is required to restrict kinesin II to the cilia middle segments. Finally, we show that, in dyf-5(lf) mutants, OSM-3 moves at a reduced speed and is not attached to IFT particles. We propose that DYF-5 plays a role in the undocking of kinesin II from IFT particles and in the docking of OSM-3 onto IFT particles.cilia length ͉ dyf-5 ͉ intraflagellar transport C ilia are present on almost every vertebrate cell and have important functions in motility or sensation. Within cilia, structural components and signaling molecules are transported by a specialized system, called intraflagellar transport (IFT) (1-5). Transport from the base of the cilia to the tip (anterograde) is mediated by kinesin-2 motor complexes, whereas dynein motor complexes mediate transport back to the base (retrograde). The nematode Caenorhabditis elegans has 60 ciliated neurons, including eight pairs of amphid neurons exposed to the environment (6). The cilia of these neurons can be divided into a middle segment with nine doublet microtubules and a distal segment with nine singlet microtubules (7). In the middle segments, two distinct kinesin-2 motor complexes mediate anterograde transport, heterotrimeric kinesin II, encoded by klp-11, klp-20, and kap-1 and homodimeric OSM-3 kinesin (8). In the distal segments, transport is mediated by only OSM-3 (8). Live imaging of the movement of these kinesins suggests that kinesin II alone moves at 0.5 m/s, and OSM-3 alone moves at 1.3 m/s, whereas the two motor complexes together move at 0.7 m/s (8). Recently, Pan et al. (9) have shown that these in vivo transport rates can be reconstituted in vitro by using purified kinesin II and OSM-3 motors. Thus far, two proteins have been identified that are required to stabilize IFT complexes transported by both kinesin II and OSM-3, BBS-7 and BBS-8 (10). However, it remains unclear how kinesin II is restricted to the cilia middle segments, whereas OSM-3 is allowed to enter the distal segments and what the functional significance is of this compartmentalization.Recently, Evans e...

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Section: Discussionmentioning

confidence: 72%

Section: Mutation Of Dyf-5 Affects Cilia Morphology and Lengthmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Mutation of the MAP kinase DYF-5 affects docking and undocking of kinesin-2 motors and reduces their speed in the cilia of Caenorhabditis elegans

Burghoorn¹,

Dekkers²,

Rademakers³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

111

181

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“…LF4 encodes a protein highly similar to mammalian male germ cell-associated kinase (Mak) and intestinal cell kinase (ICK) (13). Loss of function of the LF4 homologs Caenorhabditis elegans dye-filling defective 5 (Dyf-5) and Leishmania Mexicana LmxMPK9 also causes slightly elongated cilia or flagella (14,15). However, molecular regulatory mechanisms controlling ciliary length remain unknown.…”

mentioning

confidence: 99%

Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival

Omori

Chaya

Katoh³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

122

180

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Cilia function as cell sensors in many organs, and their disorders are referred to as "ciliopathies." Although ciliary components and transport machinery have been well studied, regulatory mechanisms of ciliary formation and maintenance are poorly understood. Here we show that male germ cell-associated kinase (Mak) regulates retinal photoreceptor ciliary length and subcompartmentalization. Mak was localized both in the connecting cilia and outer-segment axonemes of photoreceptor cells. In the Mak-null retina, photoreceptors exhibit elongated cilia and progressive degeneration. We observed accumulation of intraflagellar transport 88 (IFT88) and IFT57, expansion of kinesin family member 3A (Kif3a), and acetylated α-tubulin signals in the Mak-null photoreceptor cilia. We found abnormal rhodopsin accumulation in the Mak-null photoreceptor cell bodies at postnatal day 14. In addition, overexpression of retinitis pigmentosa 1 (RP1), a microtubule-associated protein localized in outer-segment axonemes, induced ciliary elongation, and Mak coexpression rescued excessive ciliary elongation by RP1. The RP1 N-terminal portion induces ciliary elongation and increased intensity of acetylated α-tubulin labeling in the cells and is phosphorylated by Mak. These results suggest that Mak is essential for the regulation of ciliary length and is required for the long-term survival of photoreceptors.

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Ciliogenesis associated kinase 1: targets and functions in various organ systems

Gailey

Wang

et al. 2019

FEBS Letters

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Ciliogenesis associated kinase 1 (CILK1) was previously known as intestinal cell kinase because it was cloned from that origin. However, CILK1 is now recognized as a widely expressed and highly conserved serine/threonine protein kinase. Mutations in the human CILK1 gene have been associated with ciliopathies, a group of human genetic disorders with defects in the primary cilium. In mice, both Cilk1 knock‐out and Cilk1 knock‐in mutations have recapitulated human ciliopathies. Thus, CILK1 has a fundamental role in the function of the cilium. Several candidate substrates have been proposed for CILK1 and the challenge is to relate these to the mutant phenotypes. In this review, we summarize what is known about CILK1 functions and targets, and discuss gaps in current knowledge that motivate further experimentation to fully understand the role of CILK1 in organ development in humans.

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LmxMPK9, a mitogen‐activated protein kinase homologue affects flagellar length in Leishmania mexicana

Cited by 121 publications

References 34 publications

Mutation of the MAP kinase DYF-5 affects docking and undocking of kinesin-2 motors and reduces their speed in the cilia of Caenorhabditis elegans

Mutation of the MAP kinase DYF-5 affects docking and undocking of kinesin-2 motors and reduces their speed in the cilia of Caenorhabditis elegans

Negative regulation of ciliary length by ciliary male germ cell-associated kinase (Mak) is required for retinal photoreceptor survival

Ciliogenesis associated kinase 1: targets and functions in various organ systems

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