Neuroendocrine secretory protein 55: a novel marker for the constitutive secretory pathway

The chromogranins constitute a class of acidic proteins comprising the structurally related chromogranins A and B and secretogranin II. These proteins are widely distributed in endocrine and nervous tissues; they are localized to the large dense core vesicles and released from them after stimulation of cells. In all the tissues examined chromogranins are proteolytically processed into small peptides, some of which have defined physiological activities. Chromogranin A plays a key role in large dense core vesicle biogenesis and can induce the formation of the regulated pathway. We have recently cloned neuroendocrine secretory protein 55 (NESP55), a protein that shares several features with the class of chromogranins. NESP55 is a soluble, acidic, heat-stable secretory protein that is expressed exclusively in endocrine and nervous tissues, although less widely than chromogranins. NESP55 is genomically imprinted and transcribed only from the maternal allele. It is proteolytically processed in some tissues into the small octapeptide GAIPIRRH located at the C terminus of NESP55. In the brain NESP55 is found in cell bodies and axons but not in terminals. At the subcellular level NESP55 is localized to a large vesicle, which is anterogradely transported by the fast axonal flow in neurons. From this vesicle NESP55 is constitutively released. However, in some tissues like the adrenal, medulla, and bovine splenic nerve, NESP55 is also found in the large dense transmitter storage organelles. Thus, NESP55 represents a novel peptidergic marker for a large constitutively secreting vesicle pool found in the central and peripheral nervous system.