Dense granules (also known as dense bodies or delta granules) are specialized secretory organelles. Dense granules are found only in platelets and are smaller than alpha granules. The origin of these dense granules is still unknown, however, it is thought that may come from the mechanism involving the endocytotic pathway. Dense granules are a sub group of lysosome-related organelles (LRO). There are about three to eight of these in a normal human platelet.
In unicellular organisms
They are found in animals and in unicellular organisms including Apicomplexa protozoans.
They are also found in Entamoeba.
Dense granules play a major role in Toxoplasma gondii. When the parasite invades it releases its dense granules which help to create the parasitophorous vacuole.
Toxoplasma gondii
thumb|right|Diagram of T. gondii structure with dense granules
Toxoplasma gondii contains unique organelles including dense granules.
Dense granules, along with other secretory vesicles such as a microneme and rhoptry secrete proteins involved in the gliding motility, invasion, and parasitophorous vacuole formation of T. gondii. Dense granules specifically secrete their contents several minutes after parasite invasion and localization into the parasitophorous vacuole. Proteins released from these specialized organelles are critical to adapting to the intracellular environment of the invaded host cell and contribute to parasitophorous vacuolar structure and maintenance.
Structure and biogenesis
Dense granules in T. gondii are spherical, electron dense bodies that resemble secretory vesicles in mammalian cells about 200 nm in diameter and most likely form from budding off the trans-golgi network. Dense granule (GRA) protein aggregation and retention is vital to maintaining dense granule biogenesis. This process is thought to follow the sorting-by-retention model of higher eukaryotes due to the morphological similarities of T. gondii<nowiki />'s dense granule and higher eukaryotes' dense core granules. The proposition posits that the accumulation of secretory proteins within the granules prevents their escape from maturing dense granules in the trans-golgi network by constitutive vesicle budding. Additionally, dense granule formation is clathrin dependent at the trans-golgi network. T. gondii expresses one clathrin heavy chain (CHC1) important for forming micronemes and rhoptries in T. gondii, but the adaptor important for targeting CHC1 to dense granules remains unknown. After clathrin is recruited, the mature dense granules bud off the Golgi apparatus and are shuttled to plasma membrane release sites in order to secrete their contents.
Trafficking and secretion of dense granule proteins (GRAs)
The majority of dense granule proteins or GRA proteins contain an N-terminal ER-targeting signal peptide and enter the secretory pathway via synthesis and translocation at the rough endoplasmic reticulum, and the signal sequence is thought to be cleaved off though not proven. Many GRA proteins contain a single transmembrane domain, meaning that the proteins are translocated across the endoplasmic reticulum lumen, exported to and shuttled through the Golgi apparatus, and eventually secreted from the parasite into the vacuolar space or parasitophorous vacuolar membrane. SNARE protein complexes drive the transport and docking of vesicles with proteins from the endoplasmic reticulum to the golgi body and vice versa.
Once the dense granule organelle is fully matured, the organelle appears to directly fuse with the plasma membrane between gaps of the parasite's inner membrane complex.
Functions
According to the stage of infection, the number of dense granules present in a parasite may vary from approximately 15 in tachyzoites and sporozoites, 8–10 in bradyzoites and 3–6 in merozoites. For nutrient acquisition, GRA proteins have been implicated in scavenging host lipids, such as sphingolipids from host Golgi derived vesicles, cholesterol from host endosomal or lysosomal vesicles, and other lipids from host neutral lipid droplets. GRA proteins also are involved in host protein uptake into the parasite. Further research is needed to characterize the function and prevalence of all GRA proteins.
In multicellular organisms
Components
The dense granules of human platelets contain adenosine diphosphate (ADP), adenosine triphosphate (ATP), ionized calcium (which is necessary for several steps of the coagulation cascade), and serotonin. Dense granules are similar to lysosomes with an acidic pH and even some lysosomal proteins like CD63. There is a granular adenine nucleotide pool within the dense granule. It is thought that it is made up of system of insoluble calcium. This pool is likely to be different than that of the cytoplasmic nucleotides. In some animals it has been shown that the platelets contain histamine. The patients with this disease show signs of abnormal dense granules and melanosomes which can cause prolonged bleeding and albinism. Chediak-Higashi syndrome is an autosomal recessive disorder where patients platelets have a deficient amount of dense granules. CHS is very similar to beige mouse.