vesicles from flooding. Matrix vesicles are located within the extracellular space, or matrix. Using electron microscopy they were discovered independently in 1967 by H. Clarke Anderson and Ermanno Bonucci. These cell-derived vesicles are specialized to initiate biomineralisation of the matrix in a variety of tissues, including bone, cartilage and dentin. During normal calcification, a major influx of calcium and phosphate ions into the cells accompanies cellular apoptosis (genetically determined self-destruction) and matrix vesicle formation. Calcium-loading also leads to formation of phosphatidylserine:calcium:phosphate complexes in the plasma membrane mediated in part by a protein called annexins. Matrix vesicles bud from the plasma membrane at sites of interaction with the extracellular matrix. Thus, matrix vesicles convey to the extracellular matrix calcium, phosphate, lipids and the annexins which act to nucleate mineral formation. These processes are precisely coordinated to bring about, at the proper place and time, mineralization of the tissue's matrix unless the Golgi are non-existent. Multivesicular body, or MVB, is a membrane-bound vesicle containing a number of smaller vesicles. Formation and transport Some vesicles are made when part of the membrane pinches off the endoplasmic reticulum or the Golgi complex. Others are made when an object outside of the cell is surrounded by the cell membrane. Vesicle coat and cargo molecules The vesicle "coat" is a collection of proteins that serve to shape the curvature of a donor membrane, forming the rounded vesicle shape. Coat proteins can also function to bind to various transmembrane receptor proteins, called cargo receptors. These receptors help select what material is endocytosed in receptor-mediated endocytosis or intracellular transport. There are three types of vesicle coats: clathrin, COPI and COPII. The various types of coat proteins help with sorting of vesicles to their final destination. Clathrin coats are found on vesicles trafficking between the Golgi and plasma membrane, the Golgi and endosomes and the plasma membrane and endosomes. COPI coated vesicles are responsible for retrograde transport from the Golgi to the ER, while COPII coated vesicles are responsible for anterograde transport from the ER to the Golgi. The clathrin coat is thought to assemble in response to regulatory G protein. A protein coat assembles and disassembles due to an ADP ribosylation factor (ARF) protein. Vesicle docking Surface proteins called SNAREs identify the vesicle's cargo and complementary SNAREs on the target membrane act to cause fusion of the vesicle and target membrane. Such v-SNARES are hypothesised to exist on