Sensory reception is an attribute of both primary cilia and motile cilia

Bloodgood, Robert A.

doi:10.1242/jcs.066308

Cited by 185 publications

(189 citation statements)

References 54 publications

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“…Although PAM-knockout mice fail to survive past mid-gestation, PAM heterozygotes (Pam +/− ) survive to adulthood; with half the normal level of PAM protein and activity, levels of amidated product peptides declined only slightly, suggesting that there is usually an excess of PAM activity (Bousquet-Moore et al, 2009). Nevertheless, Pam +/− mice exhibit an inability to vasoconstrict in a cold environment, increased adiposity, increased anxiety-like behavior, defects in copper homeostasis and altered synaptic transmission (Bousquet-Moore et al, 2009, 2010Gaier et al, 2010Gaier et al, , 2014. Mice maintained on a low-copper diet mirrored some of the defects observed in PAM +/− mice; several deficits were reversed by a copper-supplemented diet (Bousquet-Moore et al, 2009;Gaier et al, 2010Gaier et al, , 2014.…”

Section: The Ancestral Form Of Pam Was Membrane Tetheredmentioning

confidence: 99%

“…The importance of cilia-based signaling is demonstrated by the wide array of cilia-related disorders that occur in vertebrates (Waters and Beales, 2011;Brown and Witman, 2014). Only motile cilia can generate motive force, but both motile and primary cilia perform sensory and signaling roles (Shah et al, 2009;Bloodgood, 2010;Warner et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Early eukaryotic origins for cilia-associated bioactive peptide-amidating activity

Kumar

Blaby‐Haas

Merchant

et al. 2016

Journal of Cell Science

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Ciliary axonemes and basal bodies were present in the last eukaryotic common ancestor and play crucial roles in sensing and responding to environmental cues. Peptidergic signaling, generally considered a metazoan innovation, is essential for organismal development and homeostasis. Peptidylglycine α-amidating monooxygenase (PAM) is crucial for the last step of bioactive peptide biosynthesis. However, identification of a complete PAM-like gene in green algal genomes suggests ancient evolutionary roots for bioactive peptide signaling. We demonstrate that the Chlamydomonas reinhardtii PAM gene encodes an active peptide-amidating enzyme (CrPAM) that shares key structural and functional features with the mammalian enzyme, indicating that components of the peptide biosynthetic pathway predate multicellularity. In addition to its secretory pathway localization, CrPAM localizes to cilia and tightly associates with the axonemal superstructure, revealing a new axonemal enzyme activity. This localization pattern is conserved in mammals, with PAM present in both motile and immotile sensory cilia. The conserved ciliary localization of PAM adds to the known signaling capabilities of the eukaryotic cilium and provides a potential mechanistic link between peptidergic signaling and endocrine abnormalities commonly observed in ciliopathies.

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Section: The Ancestral Form Of Pam Was Membrane Tetheredmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Early eukaryotic origins for cilia-associated bioactive peptide-amidating activity

Kumar

Blaby‐Haas

Merchant

et al. 2016

Journal of Cell Science

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“…Indeed, as awareness grows of how diverse flagellate protists use their flagella to interact with other cells and the environment (Bloodgood 2010), it appears that it will be a rare exception to find a flagellum that does not function in some capacity as a sensory antenna. Exploiting the flagellar membrane as a surface from which to detect extracellular ligands and using a slender flagellar antenna to concentrate (i.e.…”

Section: Initially An Organelle Of Motility or Sensory Perception?mentioning

confidence: 99%

Eukaryotic Flagella: Variations in Form, Function, and Composition during Evolution

2014

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“…C ilia and flagella of eukaryotic cells are organelles that generate fluid flow on the cell surface and/or sense chemical or mechanical stimuli from the external environment (1). Cilia/flagella beating is driven by outer arm dynein (OAD) and inner arm dyneins.…”

mentioning

confidence: 99%

Cooperative binding of the outer arm-docking complex underlies the regular arrangement of outer arm dynein in the axoneme

Owa

Furuta

Usukura

et al. 2014

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

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Outer arm dynein (OAD) in cilia and flagella is bound to the outer doublet microtubules every 24 nm. Periodic binding of OADs at specific sites is important for efficient cilia/flagella beating; however, the molecular mechanism that specifies OAD arrangement remains elusive. Studies using the green alga Chlamydomonas reinhardtii have shown that the OAD-docking complex (ODA-DC), a heterotrimeric complex present at the OAD base, functions as the OAD docking site on the doublet. We find that the ODA-DC has an ellipsoidal shape ∼24 nm in length. In mutant axonemes that lack OAD but retain the ODA-DC, ODA-DC molecules are aligned in an end-to-end manner along the outer doublets. When flagella of a mutant lacking ODA-DCs are supplied with ODA-DCs upon gamete fusion, ODA-DC molecules first bind to the mutant axonemes in the proximal region, and the occupied region gradually extends toward the tip, followed by binding of OADs. This and other results indicate that a cooperative association of the ODA-DC underlies its function as the OAD-docking site and is the determinant of the 24-nm periodicity.C ilia and flagella of eukaryotic cells are organelles that generate fluid flow on the cell surface and/or sense chemical or mechanical stimuli from the external environment (1). Cilia/flagella beating is driven by outer arm dynein (OAD) and inner arm dyneins. The arrangement of dyneins on the axoneme has an overall periodicity of 96 nm, within which OAD binds every 24 nm; this 24-nm periodicity is completely conserved in essentially all eukaryotic organisms with "9 + 2" axonemes (2, 3) and even occurs in insect sperm flagella containing multiple rows of doublet microtubules arranged in a spiral configuration (4, 5). OAD is best characterized in Chlamydomonas. It is a very large protein complex of ∼2 MDa, comprising 3 heavy chains, 2 intermediate chains, and 11 distinct light chains. Most of the subunits are conserved from protists to mammals (6). OAD is the most abundant and most powerful axonemal dynein, generating about twothirds of the total propulsive force of ciliary beating (7,8). Human diseases due to ciliary motility defects [termed primary ciliary dyskinesia (PCD)] are caused most commonly by defects in OAD assembly (9-11). The assembly process and the in situ structure of the OAD complex in the axoneme have been well studied (3, 12, 13). However, the mechanism underlying the periodic binding of OAD to the doublet is poorly understood.The outer dynein arm-docking complex (ODA-DC) has been identified as a complex that mediates OAD binding to the doublet (14, 15). In the flagella of Chlamydomonas mutants (e.g., outerdynein-arm deficient oda6) retaining the ODA-DC but not OAD, the ODA-DC is observed by electron microscopy as a small projection linearly arrayed every 24 nm along the outer doublet (3,(14)(15)(16)(17). It is composed of three subunits: DC1, ∼83 kDa, encoded by ODA3; DC2, ∼62 kDa, encoded by ODA1; and DC3, ∼21 kDa, encoded by ODA14 (18-20), which assemble in the cell cytoplasm and are transported into the fla...

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Sensory reception is an attribute of both primary cilia and motile cilia

Cited by 185 publications

References 54 publications

Early eukaryotic origins for cilia-associated bioactive peptide-amidating activity

Early eukaryotic origins for cilia-associated bioactive peptide-amidating activity

Eukaryotic Flagella: Variations in Form, Function, and Composition during Evolution

Cooperative binding of the outer arm-docking complex underlies the regular arrangement of outer arm dynein in the axoneme

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