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. Originally discovered by their ability to induce the formation of bone and cartilage, BMPs are now considered to constitute a group of piv ...

(BMP) co-receptor of the

repulsive guidance molecule Repulsive guidance molecules (RGMs) are members of a three gene family (in vertebrates) composed of RGMA, RGMa, RGMB, RGMb, and hemojuvelin, RGMc (also called hemojuvelin). RGMa has been implicated to play an important role in the Neural developmen ...

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 Bone morphogenetic protein receptor type-1B also known as CDw293 (cluster of differentiation w293) is a protein that in humans is encoded by the ''BMPR1B'' gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gen ...

, 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 Bone morphogenetic protein receptor type II or BMPR2 is a serine/threonine receptor kinase. It binds Bone morphogenetic proteins, members of the TGF beta superfamily of ligands, which are involved in paracrine signalling. BMPs are involved in a ho ...

, 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 residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

is encoded by the ''RGMA''

gene In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...

Function

RGMa is a

for retinal axons. Furthermore, neogenin 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 fold become elevated, a ...

induces

apoptosis Apoptosis (from grc, ἀπόπτωσις, apóptōsis, 'falling off') is a form of programmed cell death that occurs in multicellular organisms. Biochemical events lead to characteristic cell changes (morphology) and death. These changes incl ...

. 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 cystei ...

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 Repulsive guidance molecule B (RGMb), also known as DRAGON (DRG11-responsive axonal guidance and outgrowth of neurite), is a bone morphogenetic protein (BMP) co-receptor of the repulsive guidance molecule family. In humans this protein is encoded ...

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