Stop-like Protein 21: a Novel Member of the Stop Family Revealing a Golgi Localization of Stop Proteins

Neuronal microtubules are stabilized by two calmodulin-regulated microtubule associated proteins, E-STOP and N-STOP, whose suppression in mice induces severe synaptic and behavioral deficits. Here we show that mature neurons also contain a 21 kD STOP-like protein, SL21, which shares calmodulin-binding and microtubulestabilizing homology domains with STOP proteins. Accordingly, in different biochemical or cellular assays, SL21 has calmodulin-binding and microtubulestabilizing activity. However, in cultured hippocampal neurons, SL21 antibodies principally stain the somatic Golgi and punctate Golgi material in neurites. In cycling cells, transfected SL21 decorates microtubules when expressed at high levels but is otherwise principally visible at the Golgi. The Golgi targeting of SL21 depends on the presence of cysteine residues located within the SL21 N-terminal domain, suggesting that Golgi targeting may require SL21 palmitoylation. Accordingly we find that SL21 is palmitoylated in vivo. N-STOP and E-STOP, which contain the Golgi targeting sequences present in SL21, also display distinct Golgi staining when expressed at low level in cycling cells. Thus neuronal proteins of the STOP family have capacity to associate with Golgi material, which could be important for STOP synaptic functions.