We show here that Rab27a is normally expressed in cytotoxic T lymphocytes (CTLs), but absent in ashen homozygotes (ash/ash). Cytotoxicity and secretion assays show that ash / ash CTLs are unable to kill target cells or to secrete granzyme A and hexosaminidase.

Rab27a is required for polarized secretion of lysosomes from cytotoxic T lymphocytes (CTLs) at the immunological synapse. A series of Rab27a-interacting proteins have been identified; however, only Munc13-4 has been found to be expressed in CTL.

Aug 11, 2011 · The munc13-4–rab27a complex is not needed for secretory lysosome maturation, as shown by complementation in CTLs from FHL3 patients and in a mast cell line silenced for munc13-4. In contrast, fusion of secretory lysosomes with, and content release at the plasma membrane during degranulation, strictly required the munc13-4–rab27a complex.

Nov 5, 2009 · Rab27a and Munc13-4 may become associated with lytic granules through the fusion of hetereotypic organelles with perforin-containing secretory lysosomes, as described in CTL. 32 Alternatively, effector proteins may be recruited to granules directly from the cytosol.

Dec 15, 2008 · Using a tandem affinity purification technique, we identified a previously unknown hematopoietic form of Slp2a (Slp2a-hem) and determined that it is a specific effector of the active form of Rab27a. This interaction occurs in vivo in primary CTLs.

Aug 1, 2002 · Rab27a also plays a critical role in the secretion of the granules from CTL. These cells destroy virally infected cells by releasing the contents of secretory lysosomes which include the pore forming protein, perforin, and a series of proteases which trigger apoptosis.

Dec 1, 2005 · The identification of disease-causing mutations in the small GTPase Rab27a, priming factor Munc13–4 and fusion protein syntaxin11 has defined an important role for these proteins in CTL exocytosis.

Dec 6, 2009 · The small GTPases Rab27a and Rab27b and their effectors, Slp4 and Slac2b, control exosome secretion at different steps by regulating the peripheral localization, retention and docking of...

Jan 1, 2012 · Natural Killer (NK) cells and Cytotoxic T lymphocytes (CTL) are critical for the immune response against virus infections or transformed cells. They kill target cells via polarized exocytosis of lytic proteins from secretory lysosomes (SL). Rab27a and munc13-4 interact directly and are required for target cell killing.

Dec 30, 2016 · Functional disruption of RAB27A is known to cause GS2 and its corresponding mouse model, ashen, both of which are characterized by pigment dilution in the hair and skin, due to a defect in actin-based melanosome transport, and immunodeficiency, due to a defect in CTL lytic granule exocytosis.