SAD-1 working model. (A and B) Formation of the SAD-1 complex. Expressed alone, SAD-1(S) fails to interact and cluster with STRD-1 or NAB-1 (A). When co-expressed, SAD-1(L) recruits SAD-1(S), and the SAD-1 complex binds STRD-1 and NAB-1 through the C-terminus of the long isoform (B). The interaction with STRD-1 is crucial for clustering and localizing the SAD-1 complex along the axon. The localization of STRD-1 and NAB-1 is unaffected by SAD-1 as evidenced in our previous studies. (C and D) Developmental regulation of the isoform expression. During neuronal polarization, SAD-1(L) is predominantly expressed (C). Once polarity is established, SAD-1(S) is expressed and dimer/oligomerizes with SAD-1(L) to perform a ‘surveillance’ role in synaptic organization (D).