Specific regulation of transsynaptic nanoalignment and postsynaptic assembly by a novel NCAM family synaptic adhesion molecule.

Authors

Paola Van der Linden Costello, Marina N Wennerberg, Jerrik A Rydbom, Scott Gratz, Joseph Terry, Lauren F Fennema, Kate M O'Connor-Giles, Heather T Broihier

Published in

The Journal of neuroscience : the official journal of the Society for Neuroscience. Oct 19, 2026. Epub Oct 19, 2026.

Abstract

Synapse formation underlies the organization of neurons into functional circuits and requires precise alignment and coordinated maturation of pre- and postsynaptic compartments. Many synaptogenic adhesion molecules have been identified that drive target recognition and sustained adhesion between appropriate synaptic partners. Yet the degree to which individual molecules serve distinct functions in synapse formation and maturation remains poorly understood. In particular, how exquisite nanoalignment of pre- and postsynaptic specializations flows from micron-scale adhesive interactions between synaptic partners remains a key unanswered question. Here we shed new light on this question by establishing a specialized set of synaptic functions for Epithelial limiter of Fasciclin II function (Elff), an NCAM family member with previously unknown roles in the nervous system. Our structural and functional studies at the glutamatergic Drosophila NMJ of both sexes indicate that Elff is required for postsynaptic function and maturation as well as transsynaptic alignment; however, it is not required for presynaptic function, bouton formation, or developmental expansion of the NMJ. NMJs in elff null mutants display reduced glutamate receptor clusters beginning at the embryonic stage when NMJ synapses first form. Using super-resolution STED microscopy, we demonstrate that these poorly defined postsynaptic specializations are frequently out of register with presynaptic release sites. Surprisingly, the striking defects in elff nulls occur in the context of both normal active zone number and developmental expansion of the NMJ. These findings suggest an unexpected degree of specialization among transsynaptic adhesion complexes and demonstrate that Elff-mediated signaling is critical for transsynaptic nanoarchitecture of glutamatergic synapses.Significance Statement This work reveals a surprisingly selective role for a novel NCAM family member called Elff in coordinating postsynaptic assembly and precise transsynaptic nanoalignment without altering NMJ formation, expansion or presynaptic active zone number. This separation of phenotypes is new and provides crucial insight into molecular specialization of adhesion complexes during synaptogenesis. Because NCAM family member dysfunction linked to multiple neurological disorders, most notably schizophrenia, illuminating the molecular mechanisms by which they orchestrate synaptic organization and function is an important goal.

PMID:
42896892
Bibliographic data and abstract were imported from PubMed on 20 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.