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#LAG-2

2 public questions tagged with this topic.

Which of the following describes the function of LAG-2?

LAG-2 is C. elegans Delta/Serrate/Lag2 family ligand for Notch receptors LIN-12 and GLP-1. Expressed in P2, anchor cell and primary VPC P6.p, LAG-2 extracellular DSL domain binds Notch extracellular EGF repeats triggering two proteolytic cleavages by ADAM and gamma-secretase, releasing Notch intracellular domain that complexes with LAG-1 to activate transcription. In AB lineage, LAG-2 from P2 activates GLP-1 to specify ABp fate; in vulva, LAG-2 from P6.p activates LIN-12 to specify secondary fates. Therefore general biochemical description is Notch ligand, essential for lateral and inductive Notch signaling in multiple cell fate decisions during early embryogenesis.

Ref: Henderson et al. 1994; Gilbert Chapter 4: LAG-2 functions as Notch ligand for GLP-1 and LIN-12.

What happens in embryos lacking functional LAG-2?

LAG-2 encodes Delta-like ligand for LIN-12 and GLP-1 Notch receptors. In early embryo, ABa and MS express GLP-1 while P2 presents LAG-2 and APX-1 to activate GLP-1 in ABp for A-P patterning of pharynx. In gonad, Z1.ppp/Z4.aaa require LAG-2/LIN-12 interaction to decide anchor cell versus ventral uterine fate. Without functional LAG-2, GLP-1 and LIN-12 receptors remain unbound, NICD cleavage fails, downstream targets lag-1 dependent transcription silent. Consequently ABp to ABa transformation and AC/VU defects occur, but fundamentally LIN-12 remains inactive due to absent ligand triggering, revealing ligand-dependent activation mode of Notch signaling in nematode.

Ref: Henderson et al. 1994; Gilbert Chapter 4: LAG-2 loss - LIN-12 remains inactive due to ligand absence.