Page last updated: 2024-10-24

myotube differentiation

Definition

Target type: biologicalprocess

The process in which a relatively unspecialized cell acquires specialized features of a myotube cell. Myotube differentiation starts with myoblast fusion and the appearance of specific cell markers (this is the cell development step). Then individual myotubes can fuse to form bigger myotubes and start to contract. Myotubes are multinucleated cells that are formed when proliferating myoblasts exit the cell cycle, differentiate and fuse. [GOC:mtg_muscle]

Myotube differentiation is a complex process through which myoblasts, the precursors of muscle cells, fuse together to form multinucleated myotubes, the building blocks of mature skeletal muscle. This process involves a series of coordinated events that are tightly regulated by a network of signaling pathways and transcription factors.

**1. Commitment and Proliferation of Myoblasts:**
- Myoblasts are committed to the muscle lineage and undergo extensive proliferation to increase their numbers. This process is driven by growth factors like fibroblast growth factor (FGF) and insulin-like growth factor (IGF).

**2. Withdrawal from the Cell Cycle and Induction of Differentiation:**
- Upon receiving signals from the environment, myoblasts exit the cell cycle and initiate the differentiation program. This transition involves the downregulation of cell cycle regulators and the upregulation of differentiation-specific genes.

**3. Alignment and Fusion:**
- Myoblasts align themselves along a common axis and begin to fuse together. This process requires the expression of specific adhesion molecules like cadherins and integrins, as well as the activity of cytoskeletal proteins like actin and myosin. Fusion involves the merging of plasma membranes and the formation of a shared cytoplasm, resulting in a multinucleated myotube.

**4. Myotube Maturation and Elongation:**
- Once formed, myotubes undergo a period of maturation and elongation. They synthesize and assemble muscle-specific proteins, including myosin, actin, and titin, which form the contractile apparatus. The myotubes also acquire their characteristic striated pattern due to the organization of these proteins into sarcomeres.

**5. Innervation and Functional Muscle Fiber Formation:**
- Myotubes require innervation from motor neurons to become fully functional muscle fibers. This process involves the formation of neuromuscular junctions, where motor neurons release acetylcholine that stimulates muscle contraction.

**6. Regulation of Myotube Differentiation:**
- The process of myotube differentiation is tightly regulated by a variety of signaling pathways and transcription factors, including:
- **Growth factors:** IGF, FGF
- **Transcription factors:** MyoD, Myf5, MRF4
- **Cytokines:** Interleukin-4 (IL-4), Interleukin-6 (IL-6)

**7. Role of Extracellular Matrix:**
- The extracellular matrix (ECM) surrounding myoblasts and myotubes provides structural support and signaling cues that regulate their differentiation. ECM components like laminin and fibronectin play a crucial role in promoting adhesion, migration, and fusion of myoblasts.

**8. Clinical Relevance:**
- Understanding the process of myotube differentiation is crucial for regenerative medicine and the development of therapies for muscle diseases like muscular dystrophy. By manipulating the signaling pathways and transcription factors involved in this process, it may be possible to promote muscle regeneration and repair.
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Proteins (3)

ProteinDefinitionTaxonomy
SortilinA sortilin that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q99523]Homo sapiens (human)
5'-3' exonuclease PLD3A 5-3 exonuclease PLD3 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q8IV08]Homo sapiens (human)
Vasopressin V1a receptorA vasopressin V1a receptor that is encoded in the genome of human. [PRO:WCB, UniProtKB:P37288]Homo sapiens (human)

Compounds (35)

CompoundDefinitionClassesRoles
propranololpropranolol : A propanolamine that is propan-2-ol substituted by a propan-2-ylamino group at position 1 and a naphthalen-1-yloxy group at position 3.

Propranolol: A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for MYOCARDIAL INFARCTION; ARRHYTHMIA; ANGINA PECTORIS; HYPERTENSION; HYPERTHYROIDISM; MIGRAINE; PHEOCHROMOCYTOMA; and ANXIETY but adverse effects instigate replacement by newer drugs.
naphthalenes;
propanolamine;
secondary amine
anti-arrhythmia drug;
antihypertensive agent;
anxiolytic drug;
beta-adrenergic antagonist;
environmental contaminant;
human blood serum metabolite;
vasodilator agent;
xenobiotic
relcovaptanrelcovaptan: a nonpeptide vasopressin V1 receptor antagonist; structure given in first sourceproline derivative
opc 21268OPC 21268: structure given in first source; vasopressin V1 receptor antagonist
sr 48692SR 48692: structure in first source; a neurotensin receptor-1 antagonistN-acyl-amino acid
mozavaptanmozavaptan: aquaretic agent; vasopressin V2 receptor antagonist; structure given in first sourcebenzamidesaquaretic
conivaptanconivaptan : The amide resulting from the formal condensation of 4-[(biphenyl-2-ylcarbonyl)amino]benzoic acid with the benzazepine nitrogen of 2-methyl-1,4,5,6-tetrahydroimidazo[4,5-d][1]benzazepine. It is an antagonist for two of the three types of arginine vasopressin (AVP) receptors, V1a and V2. It is used as its hydrochloride salt for the treatment of hyponatraemia (low blood sodium levels) caused by syndrome of inappropriate antidiuretic hormone (SIADH).benzazepineaquaretic;
vasopressin receptor antagonist
satavaptansatavaptan: a vasopressin V2 receptor antagonist; structure given in first source
thymidine 5'-4-nitrophenyl phosphatep-nitrophenyl thymidine 5'-monophosphate : A pyrimidine 2'-deoxyribonucleoside 5'-monophosphate that is the mono-p-nitrophenyl ester of thymidine 5'-monophosphate.

thymidine 5'-4-nitrophenyl phosphate: RN given refers to parent cpd
aryl phosphate;
C-nitro compound;
pyrimidine 2'-deoxyribonucleoside 5'-monophosphate
lixivaptan
tolvaptanbenzazepine;
benzenedicarboxamide
aquaretic;
vasopressin receptor antagonist
ritonavirritonavir : An L-valine derivative that is L-valinamide in which alpha-amino group has been acylated by a [(2-isopropyl-1,3-thiazol-4-yl)methyl]methylcarbamoyl group and in which a hydrogen of the carboxamide amino group has been replaced by a (2R,4S,5S)-4-hydroxy-1,6-diphenyl-5-{[(1,3-thiazol-5-ylmethoxy)carbonyl]amino}hexan-2-yl group. A CYP3A inhibitor and antiretroviral drug from the protease inhibitor class used to treat HIV infection and AIDS, it is often used as a fixed-dose combination with another protease inhibitor, lopinavir. Also used in combination with dasabuvir sodium hydrate, ombitasvir and paritaprevir (under the trade name Viekira Pak) for treatment of chronic hepatitis C virus genotype 1 infection as well as cirrhosis of the liver.

Ritonavir: An HIV protease inhibitor that works by interfering with the reproductive cycle of HIV. It also inhibits CYTOCHROME P-450 CYP3A.
1,3-thiazoles;
carbamate ester;
carboxamide;
L-valine derivative;
ureas
antiviral drug;
environmental contaminant;
HIV protease inhibitor;
xenobiotic
oxytocinoxytocin : A cyclic nonapeptide hormone with amino acid sequence CYIQNCPLG that also acts as a neurotransmitter in the brain; the principal uterine-contracting and milk-ejecting hormone of the posterior pituitary. Together with the neuropeptide vasopressin, it is believed to influence social cognition and behaviour.

Oxytocin: A nonapeptide hormone released from the neurohypophysis (PITUITARY GLAND, POSTERIOR). It differs from VASOPRESSIN by two amino acids at residues 3 and 8. Oxytocin acts on SMOOTH MUSCLE CELLS, such as causing UTERINE CONTRACTIONS and MILK EJECTION.
heterodetic cyclic peptide;
peptide hormone
oxytocic;
vasodilator agent
saquinavirsaquinavir : An aspartic acid derivative obtained by formal condensation of the primary amino group of (2S,3R)-4-[(3S,4aS,8aS)-3-(tert-butylcarbamoyl)octahydroisoquinolin-2(1H)-yl]-3-hydroxy-1-phenylbutan-2-ylamine with the carboxy group of N(2)(-quinolin-2-ylcarbonyl)-L-asparagine. An inhibitor of HIV-1 protease.

Saquinavir: An HIV protease inhibitor which acts as an analog of an HIV protease cleavage site. It is a highly specific inhibitor of HIV-1 and HIV-2 proteases, and also inhibits CYTOCHROME P-450 CYP3A.
L-asparagine derivative;
quinolines
antiviral drug;
HIV protease inhibitor
diethylstilbestroldiethylstilbestrol : An olefinic compound that is trans-hex-3-ene in which the hydrogens at positions 3 and 4 have been replaced by p-hydroxyphenyl groups.

Diethylstilbestrol: A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed)
olefinic compound;
polyphenol
antifungal agent;
antineoplastic agent;
autophagy inducer;
calcium channel blocker;
carcinogenic agent;
EC 1.1.1.146 (11beta-hydroxysteroid dehydrogenase) inhibitor;
EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor;
endocrine disruptor;
xenoestrogen
deaminooxytocindemoxytocin : A heterodetic cyclic peptide that is the synthetic analog of the peptide hormone oxytocin where the free amino group in the half-cystine residue is replaced by hydrogen. The mechanism of action and pharmacological properties of demoxytocin and oxytocin are similar. The drug affects the permeability of the cell membrane, increasing the content of calcium ions in smooth muscle cells, thereby increasing its contraction. It stimulates the contraction of smooth muscles of the uterus, as well as stimulating the contraction of myoepithelial cells of the mammary gland, and enhances the secretion of milk.heterodetic cyclic peptideoxytocic
arginine vasopressinArginine Vasopressin: The predominant form of mammalian antidiuretic hormone. It is a nonapeptide containing an ARGININE at residue 8 and two disulfide-linked cysteines at residues of 1 and 6. Arg-vasopressin is used to treat DIABETES INSIPIDUS or to improve vasomotor tone and BLOOD PRESSURE.

argipressin : The predominant form of mammalian vasopressin (antidiuretic hormone). It is a nonapeptide containing an arginine at residue 8 and two disulfide-linked cysteines at residues of 1 and 6.
vasopressincardiovascular drug;
hematologic agent;
mitogen
opc 51803OPC 51803: a nonpeptide vasopressin V(2)-agonist; structure in first source
atosibanoligopeptide
deamino arginine vasopressinDeamino Arginine Vasopressin: A synthetic analog of the pituitary hormone, ARGININE VASOPRESSIN. Its action is mediated by the VASOPRESSIN receptor V2. It has prolonged antidiuretic activity, but little pressor effects. It also modulates levels of circulating FACTOR VIII and VON WILLEBRAND FACTOR.heterodetic cyclic peptidediagnostic agent;
renal agent;
vasopressin receptor agonist
l 372662L 372662: structure in first source
way-151932WAY-151932: structure in first source
l 371257L 371257: structure given in first source
pmx 53
vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(o- methyl-l-tyrosine)-8-l-arginine-vasopressin, 1-(1-mercaptocyclohexaneacetic acid)-2-(O- methyl-L-tyrosine)-8-L-arginine-: highly potent antagonist of vasopressor response to arginine-vasopressin; structure in first source
l 368899
ssr 149415
gsk221149aGSK221149A: highly selective oxytocin receptor antagonist; structure in first sourcedipeptide
epelsibanepelsiban: structure in first sourcedipeptide
carbetocincarbetocin : Oxytocin in which the hydrogen on the phenolic hydroxy group is substituted by methyl, the amino group on the cysteine residue is substituted by hydrogen, and the sulfur of the cysteine residue is replaced by a methylene group. A synthetic carba-analogue of oxytocin, it is used to control bleeding after giving birth. Like oxytocin, it causes contraction of the uterus.heterodetic cyclic peptideoxytocic
neurotensinneurotensin, Tyr(11)-: RN given refers to parent cpd & (D)-isomer; RN for cpd without isomeric designation not avail 5/91peptide hormonehuman metabolite;
mitogen;
neurotransmitter;
vulnerary
nitd 609NITD 609: an antimalarial and coccidiostat; structure in first source
obe001OBE001: an oxytocin receptor antagonist
(6-chloro-1-(2-(dimethylamino)ethyl)indol-3-yl)-spiro(1h-isobenzofuran-3,4'-piperidine)-1'-yl-methanone(6-chloro-1-(2-(dimethylamino)ethyl)indol-3-yl)-spiro(1H-isobenzofuran-3,4'-piperidine)-1'-yl-methanone: a vasopressin 1a receptor antagonist; structure in first source
af38469
way 267464