Repulsive guidance molecule A (RGMa) is a

bone morphogenetic protein Bone morphogenetic proteins (BMPs) are a group of growth factors also known as cytokines and as metabologens. Professor Marshall Urist and Professor Hari Reddi discovered their ability to induce the formation of bone and cartilage, BMPs are now ...

(BMP) co-receptor of the repulsive guidance molecule family. Together with

BMPR1A The bone morphogenetic protein receptor, type IA also known as BMPR1A is a protein which in humans is encoded by the ''BMPR1A'' gene. BMPR1A has also been designated as CD292 (cluster of differentiation 292). Function The bone morphogenetic pr ...

and BMPR1B, as well as

ACVR2A Activin receptor type-2A is a protein that in humans is encoded by the ''ACVR2A'' gene. ACVR2A is an activin type 2 receptor. Function This gene encodes activin A type II receptor. Activins are dimeric growth and differentiation factors which ...

and BMPR2, it binds BMPs thereby activating the intracellular SMAD1/5/8 signalling pathway. In humans this

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 ...

is encoded by the ''RGMA''

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 ...

Function

RGMa is a repulsive guidance molecule for retinal axons. Furthermore,

neogenin Neogenin is a protein that in humans is encoded by the ''NEO1'' gene. Interactions NEO1 has been shown to interact with PTK2 PTK2 protein tyrosine kinase 2 (PTK2), also known as focal adhesion kinase (FAK), is a protein that, in humans, i ...

functions as a receptor for RGM. Neogenin overexpression and RGM downexpression in the developing embryonic

neural tube In the developing chordate (including vertebrates), the neural tube is the embryonic precursor to the central nervous system, which is made up of the brain and spinal cord. The neural groove gradually deepens as the neural folds become elevated, ...

induces

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

. The apoptotic activity of neogenin in the neural tube is associated with cleavage of its cytoplasmic domain by

caspase Caspases (cysteine-aspartic proteases, cysteine aspartases or cysteine-dependent aspartate-directed proteases) are a family of protease enzymes playing essential roles in programmed cell death. They are named caspases due to their specific cyste ...

s. RGMA belongs to a family of repulsive guidance molecules that are (glycosylphosphatidylinositol)-linked cell-membrane-associated proteins. The three proteins, RGMa (this protein), RGMb and RGMc are 40-50% identical to each other, and share similarities in predicted protein domains and overall structure. All three RGM proteins appear capable of binding selected BMPs (

s). RGMs may play inhibitory roles in prostate cancer by suppressing cell growth, adhesion, migration and invasion. RGMs can coordinate Smad-dependent and Smad-independent signalling of BMPs in prostate cancer and breast cancer cells. RGMa is also pointed as a component of the mechanisms that determine skeletal cell fusion via neogenin receptor.

Function

References

Further reading