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Molecular Mechanisms of Gastrointestinal Signaling

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Gastrointestinal Physiology

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Abstract

The epithelial cells of the gastrointestinal (GI) tract communicate with each other and with cells of other organs via a complex network of highly regulated movement of ions and biomolecules. The molecules ensure regulated activity of cells, tissues, and organs of the GI system and the body as whole. The regulated movement and subsequent activities of the biomolecules released from one cell to the target are made possible by receptive substances (receptors) localized on the membrane of the target cells or intracellular organelles, or in the cytosol. This process, which is referred to as cell-to-cell communication or cellular signaling, ensures the regulated functioning of the cells and tissues of the GI system and the whole organism. This chapter is dedicated to the mechanism of cell-to-cell communication and signaling in normal and relates it to how disease develops. Basic mechanisms of GI epithelial cell signaling and gut nutrient receptor sensing (GI chemosensation) are discussed.

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Abbreviations

5-HT:

5-hydroxytryptamine type

7TM:

Seven transmembrane

ADAM:

A disintegrin and metalloproteinase protein

Akt:

“Ak” (mouse bred) that developed thymoma (“t”)

AMPA:

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid

ANP:

Atrial natriuretic peptide

APC:

Adenomatous polyposis coli

ATF3:

Activating transcription factor 3

BMP:

Bone morphogenic protein

BNP:

Brain natriuretic peptide

CaM:

Calmodulin

CaMK:

Calcium/calmodulin-dependent protein kinases

cAMP:

Cyclic adenosine monophosphate

CaSR:

Calcium-sensing receptor of aromatic amino acid

CBPs:

Ca2+-binding proteins

CCK:

Cholecystokinin

CDK:

Cyclin-dependent kinase

CFTR:

Cystic fibrosis transmembrane conductance regulator

cGMP:

Cyclic guanosine monophosphate

CLK:

CDK-like kinase

CNP:

C-type natriuretic peptide

CO:

Carbon monoxide

CRAC:

Ca2+ release-activated Ca2+

CREB:

CAMP response element-binding protein

CSL:

(CBF1/Su(H)/Lag-1) C promoter Binding Factor-1, Suppressor of Hairless, Longevity-Assurance Gene

DAG:

Diacylglycerol

Dhh:

Desert Hedgehog

Dll-1-4:

Delta/Delta-like

Dvl or Dsh:

Disheveled

EGF:

Epidermal growth factor

EPAC:

Cyclic nucleotide-gated ion channels and exchange proteins activated by cAMP

ER:

Endoplasmic reticulum

ErbB:

Erythroblastic leukemia viral oncogene

ERK:

Extracellular receptor kinase

FABP:

Fatty acid-binding proteins

FAK:

Focal adhesion kinase

FDA:

Food and Drug Administration

FFAR:

Fatty Acid Transport Protein

FGF:

Fibroblast growth factor

FRAP1:

FK506-binding protein 12-rapamycin-associated protein 1

Fzd:

Frizzled

GABA:

Gamma-aminobutyric acid

GAG:

Glycosaminoglycan

GAPs:

GTPase-activating proteins

GBP:

GSK-3-binding proteins

GC:

Guanylate cyclase

GDI:

Guanine nucleotide dissociation inhibitor

GDNF:

Glial-derived neurotrophic factor

GDP:

Guanosine 5′-diphosphate

GEFs:

Guanine nucleotide exchange factors

GIP:

Glucose-dependent insulinotropic polypeptide

GLP-1:

Glucagon-like peptide-1

GPBAR-1:

G protein-coupled bile acid receptor 1

GPCR:

G protein (guanine nucleotide-binding protein) coupled receptor

GRKs:

GPCR kinases

GSK3:

Glycolgen synthase kinase 3

GSK-3β:

Glycogen synthase kinase-3β

GTP:

Guanosine 5′-triphosphate

HGF:

Hepatocyte growth factor

Hh:

Hedgehog

HMG:

High mobility group

HS:

Heparan sulfate

HSPGs:

Heparan sulfate proteoglycans

ICAM:

Intercellular adhesion molecules

ICD:

Intracellular domain of the notch receptor

Ig:

Immunoglobulin

IGF1R:

Insulin-like growth factor

IGF-2:

Insulin-like growth factor-2

Ihh:

Indian Hedgehog

IL:

Interleukins

ILK:

Integrin-linked kinase

IP3:

Inositol 1,4,5-trisphosphate

IP3R:

IP3 receptor

IRAG:

Nitric oxide

IRS1:

Insulin receptor substrate 1

Jag-1, Jag-2:

Jagged

JAK:

Janus kinase

LCFA:

Long-chain fatty acid

LEF:

Lymphoid enhancer factor

MAML:

Mastermind-like

MAPK:

Mitogen-activated protein kinase

M-BAR:

Membrane-type receptor for bile acids

MCT:

Medium chain triglyceride

mTOR:

Mechanistic or mammalian target of rapamycin

NAADP:

Cyclic ADP-ribose and nicotinic acid adenine dinucleotide phosphate

nAChRs:

Nicotinic acetylcholine receptors

NAD+:

Nicotinamide adenine dinucleotide

N-CAM:

Neural cell adhesion molecule

NFAT:

Nuclear factor of activated T cell

NGF:

Neuronal growth factor

NMDA:

N-methyl-d-aspartate

NO:

IP3R-associated cGMP kinase substrate

NO:

Nitric oxide

NT-3:

Neurotrophin-3

P2X receptors:

ATP-gated channels

PDGF:

Platelet-derived growth factor

PI-3-K:

Phosphoinositide-3-kinase

PIP2:

Phosphatidylinositol 4,5-bisphosphate

PKA:

Protein kinase A

PKC:

Protein kinase C

PKG:

Protein kinase G

PLC:

Phospholipase C

PPAR:

Peroxisome proliferator-activated receptors

PTB:

Phosphotyrosine binding

Ras:

Rat sarcoma

RBPJ:

Jκ immunoglobulin gene

RSTK:

Receptor serine/threonine kinase

RTK:

Receptor tyrosine kinase

SARAF:

Store-operated calcium entry-associated regulatory factor

SCF (also called c-kit):

Stem cell factor

SCFA:

Short chain fatty acid

SGLT1:

Sodium glucose cotransporter type 1

SH2:

Src homology 2

Shh:

Sonic hedgehog

Shh:

Sonic Hedgehog

SIM:

Stromal interacting molecule (previous name for STIMI1)

SOCE:

Store-operated calcium channel

STa:

Bacterial heat-stable enterotoxins

STAT:

Signal transducers and activators of transcription

STIM1:

Stromal interaction molecule 1

TCF:

T cell factor

TGF-beta:

Transforming growth factor beta

TKI:

Tyrosine kinase inhibitors

TMEM66:

Transmembrane protein 66

TNFs:

Tumor necrosis factors

TRP:

Transient Receptor Potential

TRPV1:

Transient Receptor Potential Valinoid type 1

TSC1-TSC2:

Tuberous sclerosis complex subunit 1 and 2

VCAM:

Vascular cell adhesion molecule

VEGF:

Vascular endothelial growth factor

Wif-1 & 2:

Wnt inhibitory factor 1 and 2

Wnt:

Wingless-related integration site

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  1. Department of Physiology, Faculty of Basic Medical Sciences, College of Health Sciences, Nile University of Nigeria, FCT-Abuja, Nigeria

    Menizibeya Osain Welcome MD, PhD

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Welcome, M.O. (2018). Molecular Mechanisms of Gastrointestinal Signaling. In: Gastrointestinal Physiology. Springer, Cham. https://doi.org/10.1007/978-3-319-91056-7_5

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