Extracellular proteolysis at the synapses: a key to neuronal plasticity

Prolactin receptor is membrane receptor without internal enzymatic activity, functioning via cytosolic tyro-sine kinases. Two large domains: extracellular prolactin binding and intracellular are linked by a short trans-membrane. Prolactin connection to receptor changes extracellular domain conformation, leading to vicinal receptors dimerisation. Receptors dimer activates cy-tosolic tyrosine kinase which phosphorylates intrac-ellular domain of receptor leading to specific protein incorporation. The hypothesis that prolactin receptor features depend on peptide chain length and alternative splicing is studied widely. Different subtypes of the prolactin receptor are present in same type of cells in vivo and their expression is regulated hormonally. It is known that mouse liver PRL receptor is composed of many proteins. Two of them were synthesized and described as receptor precursors of 292 and 303 amino acids. Such proteins have common signalling sequences , extracellular and transmembrane domains. Part of their cytoplasmic domain is identical, differing only in terminal part. Different mRNA for prolactin receptor is coded by at least two genes while total amount of receptor proteins is result of alternative splicing. Such process causes different physiological and molecular functions of prolactin dependent on various types of receptors involved in different signalling pathway from other PRL receptors. In human cells short receptor forms of prolactin are found. Receptors isoforms are similar in case of humans and rodents but human prolactin receptor short form composition is unique. This receptor form rivals with signalling pathway of the long form making tissue less sensitive to ligand. Wide spread of short forms of receptors suggests that tissues can use them as " traps " in highly concentrated lactogens in pregnancy and lactation. It is also probable that short form-receptors activate different signalling pathways in some cells or species. Last studies show that short form of receptor via own signalling pathway, leads to repression of transcription factor FOXO3 and the target gene GALT creating serious ovary defect. New active human prolactin isoform receptor containing only one extracellular, fibronectin-like domain also was examined. Alternative human receptor gene splicing to 11 exon induces the formation of many isoforms of this receptor and prolactin binding proteins, causing various distribution of these receptors in tissues differentiating a molecular action of prolactin. Further research can give information on complexity and multidirectional regulatory action of the prolactin. Matrix metalloproteinase 9 (MMP-9) is an extracellularly operating enzyme that has recently been implicated in dendritic remodeling, synaptic plasticity, learning and Furthermore, MMP-9 has been …