Disease relevance of Sybl1

• Here we show that compartments of the late endocytic pathway, bearing the tetanus neurotoxin-insensitive vesicle-associated membrane protein (TI-VAMP/VAMP7), are recruited upon particle binding and undergo exocytosis before phagosome sealing in macrophages during Fc receptor (FcR)-mediated phagocytosis [1].

High impact information on Sybl1

• TI-VAMP/VAMP7 is required for optimal phagocytosis of opsonised particles in macrophages [1].
• In addition, inhibition of TI-VAMP activity led to a reduced exocytosis of late endocytic vesicles and this resulted in an early blockade of pseudopod extension, as observed by scanning electron microscopy [1].
• In c-Fos-deficient mast cells, we found that FcepsilonRI-mediated degranulation was significantly inhibited, which correlates with the reduced expression of SWAP-70, VAMP-7, and Synaptotagmin I genes, which are involved directly in the degranulation process [2].
• Furthermore, TI-VAMP- but not synaptobrevin 2-containing vesicles accumulated at the site of the L1 bead-cell junction [3].
• Plasma membrane L1 was internalized into the TI-VAMP-containing compartment [3].

Biological context of Sybl1

• Therefore, TI-VAMP defines a new pathway of membrane delivery required for optimal FcR-mediated phagocytosis [1].

Anatomical context of Sybl1

• L1, a cell-cell adhesion molecule involved in axonal outgrowth, colocalized with TI-VAMP in the developing brain, neurons in culture, and PC12 cells [3].
• Here we show that the expression of the N-terminal domain of TI-VAMP inhibits the outgrowth of both dendrites and axons in neurons in primary culture [4].

Physical interactions of Sybl1

• TI-VAMP interacts with plasma membrane and endosomal target soluble N-ethylmaleimide-sensitive factor attachment protein receptors, suggesting that TI-VAMP mediates a recycling pathway [3].

Other interactions of Sybl1

• Finally, using the extracellular domain of L1 and N-cadherin immobilized on beads, we found that the silencing of TI-VAMP led to impaired L1- but not N-cadherin-mediated adhesion [3].

Analytical, diagnostic and therapeutic context of Sybl1

• Finally, sequence analysis indicates that a similar domain is likely present in the endosomal/lysosomal SNARE VAMP7 [5].

References