Fasciclin 2 (Fas2 or FasII) is a 95

kilodalton The dalton or unified atomic mass unit (symbols: Da or u, respectively) is a unit of mass defined as of the mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state and at rest. It is a non-SI unit accepted f ...

cell membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

glycoprotein Glycoproteins are proteins which contain oligosaccharide (sugar) 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 a ...

in the

immunoglobulin An antibody (Ab) or immunoglobulin (Ig) is a large, Y-shaped protein belonging to the immunoglobulin superfamily which is used by the immune system to identify and neutralize antigens such as pathogenic bacteria, bacteria and viruses, includin ...

(Ig) – related superfamily of

cell adhesion molecules Cell adhesion molecules (CAMs) are a subset of cell surface proteins that are involved in the binding of cells with other cells or with the extracellular matrix (ECM), in a process called cell adhesion. In essence, CAMs help cells stick to each ...

(CAMs).L.V. Kristiansen and M. Hortsch: Fasciclin II: The NCAM Ortholog in Drosophila melanogaster. In: Structure and Function of the Neural Cell Adhesion Molecule NCAM, Series: Advances in Experimental Medicine and Biology, Vol. 663, pp. 387-401, V. Berezin (Ed.), 2010, XVI, 436 p., 67 illus., Springer, Hardcover, It was first identified in the developing

grasshopper Grasshoppers are a group of insects belonging to the suborder Caelifera. They are amongst what are possibly the most ancient living groups of chewing herbivorous insects, dating back to the early Triassic around 250 million years ago. Grassh ...

embryo 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 sp ...

, seen dynamically expressed on a subset of fasciculating

axons An axon (from Greek ἄξων ''áxōn'', axis) or nerve fiber (or nerve fibre: see spelling differences) is a long, slender projection of a nerve cell, or neuron, in vertebrates, that typically conducts electrical impulses known as action pot ...

in the

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain, spinal cord and retina. The CNS is so named because the brain integrates the received information and coordinates and influences the activity o ...

(CNS), functioning as a neuronal recognition molecule in the regulation of selective axon fasciculation. Subsequently, fasII was cloned and has mainly been studied in the fruit fly (''

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...

''). Its

extracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

structure consists of two

Fibronectin type III domain The Fibronectin type III domain is an evolutionarily conserved protein domain that is widely found in animal proteins. The fibronectin protein in which this domain was first identified contains 16 copies of this domain. The domain is about 100 am ...

s and five Ig-like

C2 domain A C2 domain is a protein structural domain involved in targeting proteins to cell membranes. The typical version (PKC-C2) has a beta-sandwich composed of 8 β-strands that co-ordinates two or three calcium ions, which bind in a cavity formed by th ...

s, having structural homology to the

neural cell adhesion molecule Neural cell adhesion molecule (NCAM), also called CD56, is a homophilic binding glycoprotein expressed on the surface of neurons, glia and skeletal muscle. Although CD56 is often considered a marker of neural lineage commitment due to its discover ...

(NCAM) found in

vertebrates Vertebrates () are animals with a vertebral column (backbone or spine), and a cranium, or skull. The vertebral column surrounds and protects the spinal cord, while the cranium protects the brain. The vertebrates make up the subphylum Vertebra ...

Alternative splicing Alternative splicing, alternative RNA splicing, or differential splicing, is an alternative RNA splicing, splicing process during gene expression that allows a single gene to produce different splice variants. For example, some exons of a gene ma ...

of fasII gives rise to its expression in three major

isoforms A protein isoform, or "protein variant", is a member of a set of highly similar proteins that originate from a single gene and are the result of genetic differences. While many perform the same or similar biological roles, some isoforms have uniqu ...

, including a membrane-associated form that is attached to the outer leaflet of the

plasma membrane The cell membrane (also known as the plasma membrane or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of a cell from the outside environment (the extr ...

via a

glycophosphatidylinositol Glycosylphosphatidylinositol () or glycophosphatidylinositol (GPI) is a phosphoglyceride that can be attached to the C-terminus of a protein during posttranslational modification. The resulting GPI-anchored proteins play key roles in a wide vari ...

(GPI anchor) linkage and two integral transmembrane forms. The larger transmembrane form has an

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 a ...

motif contained in its cytoplasmic domain that is rich in

proline Proline (symbol Pro or P) is an organic acid classed as a proteinogenic amino acid (used in the biosynthesis of proteins), although it does not contain the amino group but is rather a secondary amine. The secondary amine nitrogen is in the p ...

glutamic acid Glutamic acid (symbol Glu or E; known as glutamate in its anionic form) is an α- amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can ...

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − ...

and

threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form when dissolved in water), a carboxyl group (which is in the deprotonated −COO− ...

residues (

PEST sequence A PEST sequence is a peptide sequence that is rich in proline (P), glutamic acid (E), serine (S) and threonine (T). It is associated with proteins that have a short intracellular half-life, so might act as a signal peptide for protein degradation. ...

). The fasciclin 1 (Fas1) and fasciclin 3 (Fas3) genes in ''Drosophila'' also code for cell adhesion proteins in the nervous system but do not show any structural or functional similarities with NCAM. FasII is initially expressed selectively localized to basolateral junctions during the process of

oogenesis Oogenesis () or ovogenesis is the differentiation of the ovum (egg cell) into a cell competent to further develop when fertilized. It is developed from the primary oocyte by maturation. Oogenesis is initiated before birth during embryonic devel ...

, where it functions to establish

polarity Polarity may refer to: Science *Electrical polarity, direction of electrical current *Polarity (mutual inductance), the relationship between components such as transformer windings *Polarity (projective geometry), in mathematics, a duality of orde ...

in inner polar cells of

epithelium Epithelium or epithelial tissue is a thin, continuous, protective layer of cells with little extracellular matrix. An example is the epidermis, the outermost layer of the skin. Epithelial ( mesothelial) tissues line the outer surfaces of man ...

-derived

border cells The border cells are a cluster of 6–8 cells that migrate in the ovariole of the fruit-fly ''Drosophila melanogaster'', during the process of oogenesis. A fly ovary consists of a string of ovarioles or egg chambers arranged in an increasing orde ...

. 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 ...

, fasII is dynamically expressed on a subset of axon fascicles in longitudinal nervous system pathways,Sanes, Dan Harvey., Thomas A. Reh, and William A. Harris. Development of the Nervous System. Burlington, MA: Academic, 2012. Print. including the MP1 tract. Here, fasII (and other attractive/repulsive environmental cues such as

semaphorins Semaphorins are a class of secreted and membrane proteins that were originally identified as axonal growth cone guidance molecules. They primarily act as short-range inhibitory signals and signal through multimeric receptor (biochemistry), recepto ...

and other

morphogens A morphogen is a substance whose non-uniform distribution governs the Natural patterns, pattern of tissue development in the process of morphogenesis or pattern formation, one of the core processes of developmental biology, establishing positio ...

) functions as a framework for pathfinding choices of newly extending axons. This is achieved through trans-homophilic fasII-mediated adhesion and subsequent activation of downstream

intracellular signaling In biology, cell signaling (cell signalling in British English) is the Biological process, process by which a Cell (biology), cell interacts with itself, other cells, and the environment. Cell signaling is a fundamental property of all Cell (biol ...

pathways involving

mitogen-activated protein kinase A mitogen-activated protein kinase (MAPK or MAP kinase) is a type of serine/threonine-specific protein kinases involved in directing cellular responses to a diverse array of stimuli, such as mitogens, osmotic stress, heat shock and proinflamma ...

(MAPK) and regulation of

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

calcium Calcium is a chemical element; it has symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to it ...

levels. Later, fasII is expressed on

growth cones Growth may refer to: Biology *Auxology, the study of all aspects of human physical growth *Bacterial growth *Cell growth *Growth hormone, a peptide hormone that stimulates growth *Human development (biology) *Plant growth *Secondary growth, growt ...

of axons in other tracts including embryonic

peripheral nervous system The peripheral nervous system (PNS) is one of two components that make up the nervous system of Bilateria, bilateral animals, with the other part being the central nervous system (CNS). The PNS consists of nerves and ganglia, which lie outside t ...

(PNS)

motor neurons A motor neuron (or motoneuron), also known as efferent neuron is a neuron whose cell body is located in the motor cortex, brainstem or the spinal cord, and whose axon (fiber) projects to the spinal cord or outside of the spinal cord to directly or ...

. Only the transmembrane isoforms are expressed by

neurons A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural net ...

, while the GPI-linked form is expressed by non-neuronal cells (mainly

glial cells Glia, also called glial cells (gliocytes) or neuroglia, are non-neuronal cells in the central nervous system (the brain and the spinal cord) and in the peripheral nervous system that do not produce electrical impulses. The neuroglia make up ...

), where it functions as a

substrate Substrate may refer to: Physical layers *Substrate (biology), the natural environment in which an organism lives, or the surface or medium on which an organism grows or is attached ** Substrate (aquatic environment), the earthy material that exi ...

for growth cones of extending axons, directing adhesion and axon guidance. FasII is also expressed by clusters of differentiating neuroblasts at early stages of

neurogenesis Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). This occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells ( ...

where its function is not fully understood but might be involved in proneural gene induction. Other roles for fasII include delineating two axonal pathways in the adult ocellar sensory system (OSS) via its expression on ocellar pioneer (OP) neurons where it acts to promote

neurite A neurite or neuronal process refers to any projection from the cell body of a neuron. This projection can be either an axon or a dendrite. The term is frequently used when speaking of immature or developing neurons, especially of cells in culture ...

outgrowth from primary neurons (along with neuroglian) by activating

fibroblast growth factor receptor The fibroblast growth factor receptors (FGFR) are, as their name implies, receptors that bind to members of the fibroblast growth factor (FGF) family of proteins. Some of these receptors are involved in pathological conditions. For example, a po ...

(FGFR) signaling. In addition, fasII has been shown to be involved in synaptic target selection, stabilization and remodeling along with several proteins such as

netrins Netrins are a class of proteins involved in axon guidance. They are named after the Sanskrit word "netr", which means "one who guides". Netrins are genetically conserved across nematode worms, fruit flies, frogs, mice, and humans. Structurally ...

, semaphorins and other Ig-CAMs. The human homolog is

STAB2 Stabilin-2 is a protein that in humans is encoded by the ''STAB2'' gene. Function This gene encodes a large, transmembrane receptor protein which may function in angiogenesis, lymphocyte homing, cell adhesion, or receptor scavenging. The prote ...

References

{{reflist Glycoproteins Cell adhesion molecules

See also

References