Endogenous β-neurexins on axons and within synapses show regulated dynamic behavior
Oliver Klatt,
Daniele Repetto,
Johannes Brockhaus,
Carsten Reissner,
Abderazzaq El khallouqi,
Astrid Rohlmann,
Martin Heine,
Markus Missler
Affiliations
Oliver Klatt
Institute of Anatomy and Molecular Neurobiology, Westfälische Wilhelms-University, 48149 Münster, Germany; Functional Neurobiology Group, Institute for Developmental Biology and Neurobiology, Johannes Gutenberg University, 55128 Mainz, Germany
Daniele Repetto
Institute of Anatomy and Molecular Neurobiology, Westfälische Wilhelms-University, 48149 Münster, Germany
Johannes Brockhaus
Institute of Anatomy and Molecular Neurobiology, Westfälische Wilhelms-University, 48149 Münster, Germany
Carsten Reissner
Institute of Anatomy and Molecular Neurobiology, Westfälische Wilhelms-University, 48149 Münster, Germany
Abderazzaq El khallouqi
Functional Neurobiology Group, Institute for Developmental Biology and Neurobiology, Johannes Gutenberg University, 55128 Mainz, Germany
Astrid Rohlmann
Institute of Anatomy and Molecular Neurobiology, Westfälische Wilhelms-University, 48149 Münster, Germany
Martin Heine
Functional Neurobiology Group, Institute for Developmental Biology and Neurobiology, Johannes Gutenberg University, 55128 Mainz, Germany; Corresponding author
Markus Missler
Institute of Anatomy and Molecular Neurobiology, Westfälische Wilhelms-University, 48149 Münster, Germany; Corresponding author
Summary: Neurexins are key organizer molecules that regulate synaptic function and are implicated in autism and schizophrenia. β-neurexins interact with numerous cell adhesion and receptor molecules, but their neuronal localization remains elusive. Using single-molecule tracking and high-resolution microscopy to detect neurexin1β and neurexin3β in primary hippocampal neurons from knockin mice, we demonstrate that endogenous β-neurexins are present in fewer than half of excitatory and inhibitory synapses. Moreover, we observe a large extrasynaptic pool of β-neurexins on axons and show that axonal β-neurexins diffuse with higher surface mobility than those transiently confined within synapses. Stimulation of neuronal activity further increases the mobility of synaptic and axonal β-neurexins, whereas inhibition causes the opposite. Blocking ectodomain cleavage by metalloproteases also reduces β-neurexin mobility and enhances glutamate release. These findings suggest that the surface mobility of endogenous β-neurexins inside and outside of synapses is dynamically regulated and linked to neuronal activity.
