Anosmin-1 is a secreted,
EM associated glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycos ...
found in
humans and other
organisms responsible for normal
development, which is expressed in the brain, spinal cord and kidney. Absence or damage to the protein results in
Kallmann syndrome in humans, which is characterized by loss of
olfactory bulbs and
GnRH secretion leading to
anosmia and
hypothalamic
The hypothalamus () is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus i ...
hypogonadotropic hypogonadism. Anosmin-1 is coded by the
KAL-1 gene, which is found on the
X chromosome. Anosmin-1 is 100
kilodaltons and is expressed on the outside of cells. Because of this and because of its contribution to normal migration of
nerve cells, a role in the
extracellular matrix has been postulated.
During
neural crest cell development, anosmin-1 plays a role in cranial neural cell formation by spatiotemporal regulation.
Secreated anosmin-1 enhances
FGF activity by promoting FGF8-FGFR1 complex formation, whereas inhibits both
BMP5
Bone morphogenetic protein 5 is a protein that in humans is encoded by the ''BMP5'' gene.
The protein encoded by this gene is member of the TGFβ superfamily. Bone morphogenetic proteins are known for their ability to induce bone and cartilage d ...
and
WNT3A
Protein Wnt-3a is a protein that in humans is encoded by the ''WNT3A'' gene.
The WNT gene family consists of structurally related genes that encode secreted signaling proteins. These proteins have are critical in tissue homeostasis, embryonic de ...
activities.
As a results, orchestrated regulation of FGF, BMP, and WNT by anosmin-1 control
EMT and
MET during neural crest cell development.
In human retinal pigment epithelial cell (RPE), the expression of anosmin-1 is regulated by
TGF-β which remain to be investigated.
Anosmin-1 is encoded by a gene ''ANOS1'' (earlier called ''ADMLX, KAL, KAL1, KALIG1''). In human it is located on the
X chromosome at Xp22.3 and is affected in some male individuals with
Kallmann syndrome.
This gene codes for a
protein of the
extracellular matrix named anosmin-1, which is involved in the migration of certain
nerve cell precursors (neuroendocrine GnRH cells) during
embryogenesis
An embryo is an initial stage of development of 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 sperm ...
.
Deletion
Deletion or delete may refer to:
Computing
* File deletion, a way of removing a file from a computer's file system
* Code cleanup, a way of removing unnecessary variables, data structures, cookies, and temporary files in a programming language
* ...
or
mutation of this gene results in loss of the functional protein and affects the proper development of the
olfactory nerves
The olfactory nerve, also known as the first cranial nerve, cranial nerve I, or simply CN I, is a cranial nerve that contains sensory nerve fibers relating to the sense of smell.
The afferent nerve fibers of the olfactory receptor neurons tr ...
and
olfactory bulbs
The olfactory bulb (Latin: ''bulbus olfactorius'') is a neural structure of the vertebrate forebrain involved in olfaction, the sense of smell. It sends olfactory information to be further processed in the amygdala, the orbitofrontal cortex (OFC ...
. In addition, neural cells that produce
GnRH fail to migrate to the
hypothalamus.
Clinically, mutation results in the
X-linked form of Kallmann syndrome. Individuals with Kallmann syndrome experience
anosmia (lack of smell) and do not go through
puberty (hypothalamic
hypogonadotropic hypogonadism).
ANOS1 is made of 14
exon
An exon is any part of a gene that will form a part of the final mature RNA produced by that gene after introns have been removed by RNA splicing. The term ''exon'' refers to both the DNA sequence within a gene and to the corresponding sequen ...
s and spans 120-200
kilobases. Mutations of ANOS1 may account for 14% of the cases of familial Kallmann syndrome and 11% of male sporadic cases.
References
{{reflist
External links
GeneReviews/NCBI/NIH/UW entry on Kallmann syndromeNextBio.comGenAtlas
Proteins