Dynein axonemal heavy chain 11 (DNAH11) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that is encoded by the ''DNAH11''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

in humans. In mice, the protein is encoded by the ''Dnahc11'' gene, the murine homolog to human ''DNAH11.''Lucas, J. S., Adam, E. C., Goggin, P. M., Jackson, C. L., Powles‐Glover, N., Patel, S. H., ... & Lackie, P. M. (2012). Static respiratory cilia associated with mutations in Dnahc11/DNAH11: a mouse model of PCD. Human mutation, 33(3), 495-503. https://doi.org/10.1002/humu.22001 The protein was previously known as 'left-right' dynein (with the corresponding gene alias ''lrd'') in mice and is particularly notable during

embryogenesis An embryo ( ) is the initial stage of development for a multicellular organism. In organisms that reproduce sexually, embryonic development is the part of the life cycle that begins just after fertilization of the female egg cell by the male ...

for orientation of the eventual

body plan A body plan, (), or ground plan is a set of morphology (biology), morphological phenotypic trait, features common to many members of a phylum of animals. The vertebrates share one body plan, while invertebrates have many. This term, usually app ...

Function

This gene encodes a member of the

dynein Dyneins are a family of cytoskeletal motor proteins (though they are actually protein complexes) that move along microtubules in cells. They convert the chemical energy stored in ATP to mechanical work. Dynein transports various cellular cargo ...

heavy chain family, DNAH11, a

microtubule Microtubules are polymers of tubulin that form part of the cytoskeleton and provide structure and shape to eukaryotic cells. Microtubules can be as long as 50 micrometres, as wide as 23 to 27 nanometer, nm and have an inner diameter bet ...

-dependent motor

ATPase ATPases (, Adenosine 5'-TriPhosphatase, adenylpyrophosphatase, ATP monophosphatase, triphosphatase, ATP hydrolase, adenosine triphosphatase) are a class of enzymes that catalyze the decomposition of ATP into ADP and a free phosphate ion or ...

protein critical for processes involving ciliary movement. The

''DNAH11'' has reported associations in a number of important

physiological Physiology (; ) is the science, scientific study of function (biology), functions and mechanism (biology), mechanisms in a life, living system. As a branches of science, subdiscipline of biology, physiology focuses on how organisms, organ syst ...

processes including the movement of respiratory cilia,

sperm Sperm (: sperm or sperms) is the male reproductive Cell (biology), cell, or gamete, in anisogamous forms of sexual reproduction (forms in which there is a larger, female reproductive cell and a smaller, male one). Animals produce motile sperm ...

motility, and establishment of the adult

. A knockout model of this gene has not been reported.

Embryogenesis

The body plan is naturally

asymmetrical Asymmetry is the absence of, or a violation of, symmetry (the property of an object being invariant to a transformation, such as reflection). Symmetry is an important property of both physical and abstract systems and it may be displayed in pre ...

, and the overall order is defined during embryonic

gastrulation Gastrulation is the stage in the early embryonic development of most animals, during which the blastula (a single-layered hollow sphere of cells), or in mammals, the blastocyst, is reorganized into a two-layered or three-layered embryo known as ...

in mammals where the three

germ layer A germ layer is a primary layer of cell (biology), cells that forms during embryonic development. The three germ layers in vertebrates are particularly pronounced; however, all eumetazoans (animals that are sister taxa to the sponges) produce tw ...

s (

endoderm Endoderm is the innermost of the three primary germ layers in the very early embryo. The other two layers are the ectoderm (outside layer) and mesoderm (middle layer). Cells migrating inward along the archenteron form the inner layer of the gastr ...

mesoderm The mesoderm is the middle layer of the three germ layers that develops during gastrulation in the very early development of the embryo of most animals. The outer layer is the ectoderm, and the inner layer is the endoderm.Langman's Medical ...

, and

ectoderm The ectoderm is one of the three primary germ layers formed in early embryonic development. It is the outermost layer, and is superficial to the mesoderm (the middle layer) and endoderm (the innermost layer). It emerges and originates from the o ...

) are established. At the beginnings of gastrulation, the

primitive node The primitive node (or primitive knot) is the organizer for gastrulation in most amniote embryos. In birds, it is known as Hensen's node, and in amphibians, it is known as the Spemann-Mangold organizer. It is induced by the Nieuwkoop center in ...

serves as the organizer and has motile cilia on its surface. These cilia are responsible for directing increased amounts of

nodal Nodal may refer to: * Nodal, the adjectival form of the noun :wikt:node * Nodal homolog, a protein encoded by the gene NODAL and responsible for left-right asymmetry * Nodal (software), a novel music composition program * Christian Nodal ( ...

to the left side of the developing embryo, establishing asymmetry. For this reason, proper expression of ''DNAH11'' is critical for correct establishment and subsequent development of the asymmetrical body plan.

Clinical significance

Primary ciliary dyskinesia

Mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s in this ''DNAH11'' have been implicated in causing

Primary Ciliary Dyskinesia Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive genetic ciliopathy, that causes defects in the action of cilia lining the upper and lower respiratory tract, sinuses, Eustachian tube, middle ear, fallopian tube, and flagella of spe ...

(PCD), formerly called 'immotile cilia syndrome', and results from abnormally motile or static cilia within the respiratory tract. PCD is characterized by bronchiectasis, frequent upper respiratory tract infections, and issues with fertility, and PCD individuals have increased rates of

heterotaxy Situs ambiguus (), or heterotaxy, is a rare congenital defect in which the major visceral organs are distributed abnormally within the chest and abdomen. Clinically, heterotaxy spectrum generally refers to any defect of left-right asymmetry and a ...

and ''

situs inversus ''Situs inversus'' (also called ''situs transversus'' or ''oppositus'') is a Congenital disorder, congenital condition in which the major Organ (anatomy), visceral organs are reversed or mirror image, mirrored from their normal positions. The norm ...

'' in approximately 50% of reported cases'','' a

congenital A birth defect is an abnormal condition that is present at childbirth, birth, regardless of its cause. Birth defects may result in disability, disabilities that may be physical disability, physical, intellectual disability, intellectual, or dev ...

condition in which some organs are mirrored to an abnormal side of the body cavity. Mutations in ''DNAH11'' are also associated with

Kartagener syndrome Primary ciliary dyskinesia (PCD) is a rare, autosomal recessive genetic ciliopathy, that causes defects in the action of cilia lining the upper and lower respiratory tract, sinuses, Eustachian tube, middle ear, fallopian tube, and flagella of ...

(PCD with ''situs inversus totalis,'' a congenital condition with a characteristic total inversion of the body plan and organs).

Fertility

Genetic errors with ''DNAH11'' have been shown to cause a number of fertility-related effects in both sexes. Decreased motile cilia-specific expression of ''DNAH11'' within the

axoneme In molecular biology, an axoneme, also called an axial filament, is the microtubule-based cytoskeletal structure that forms the core of a cilium or flagellum. Cilia and flagella are found on many cells, organisms, and microorganisms, to pr ...

of sperm is associated with lower levels of sperm motility. For this reason, males with PCD are not sterile, but they are often

infertile In biology, infertility is the inability of a male and female organism to reproduce. It is usually not the natural state of a healthy organism that has reached sexual maturity, so children who have not undergone puberty, which is the body's sta ...

under conventional methods due to lack of sperm

motility Motility is the ability of an organism to move independently using metabolism, metabolic energy. This biological concept encompasses movement at various levels, from whole organisms to cells and subcellular components. Motility is observed in ...

; however, there are cases of ''DNAH11'' mutant males fathering offspring without intervention of

assisted reproductive technologies Assisted reproductive technology (ART) includes medical procedures used primarily to address infertility. This subject involves procedures such as in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI), and cryopreservation of gamet ...

. In females with PCD or Kartagener's syndrome, there are increased reports of subfertility and risk of

ectopic pregnancy Ectopic pregnancy is a complication of pregnancy in which the embryo attaches outside the uterus. Signs and symptoms classically include abdominal pain and vaginal bleeding, but fewer than 50 percent of affected women have both of these sympto ...

. Because females'

fallopian tube The fallopian tubes, also known as uterine tubes, oviducts or salpinges (: salpinx), are paired tubular sex organs in the human female body that stretch from the Ovary, ovaries to the uterus. The fallopian tubes are part of the female reproduct ...

s are lined with motile cilia which show identical motor protein composition to those observed in the

respiratory tract The respiratory tract is the subdivision of the respiratory system involved with the process of conducting air to the alveoli for the purposes of gas exchange in mammals. The respiratory tract is lined with respiratory epithelium as respirato ...

, this is believed to result in the increased risks observed in case studies (although affected PCD females' cilia have not been directly analyzed so this remains inconclusive).

References

External links

GeneReviews/NCBI/NIH/UW entry on Primary Ciliary Dyskinesia
{{Ciliary proteins