CLASP1/2 REGULATE IMMUNE SYNAPSE MATURATION IN NATURAL KILLER CELLS.

Area of Science:

• Immunology
• Cell Biology

Background:

• Natural killer (NK) cells are vital for innate immunity against viral infections and tumors.
• Immune synapse (IS) formation is critical for NK cell cytotoxic activity.
• Lymphocyte function-associated antigen (LFA)-1 organization at the IS is Golgi-dependent but not fully understood.

Purpose of the Study:

• To investigate the role of CLIP-associating proteins (CLASP) 1/2 in NK cell immune synapse (IS) maturation.
• To elucidate the mechanism of LFA-1 organization at the IS.
• To explore the function of Golgi-derived microtubules (GDMTs) in NK cell cytotoxicity.

Main Methods:

• Depletion of CLASP1/2 in NK cells.
• Analysis of LFA-1 organization at the IS.
• Assessment of centrosome and lytic granule polarization.
• Investigation of microtubule nucleation at the Golgi apparatus.

Main Results:

• CLASP1/2 depletion impaired LFA-1 organization at the IS.
• CLASP1/2 depletion inhibited centrosome and lytic granule polarization towards target cells.
• The Golgi apparatus functions as a microtubule organizing center (MTOC) in NK cells.
• NK cells require CLASP1/2 and AKAP350 for efficient microtubule nucleation at the Golgi.

Conclusions:

• CLASP1/2 plays a critical role in the maturation of the lytic IS in NK cells.
• Golgi-derived microtubules (GDMTs) contribute to IS maturation.
• CLASP1/2-mediated stabilization of GDMTs facilitates LFA-1 trafficking for IS maturation.